Association of p73 G4C14?A4T14 and p53 codon 72 polymorphism with cervical cancer in Chinese population

Background: Cervical cancer is known to be the fourth most common cancer among women globally. In various factors, genetic factors have been considered as one major risk factor for cervical cancer. The research of genetic susceptibility to cervical cancer can be greatly helpful in studying the complex mechanism. This study was conducted to identify whether polymorphic variants of p73 G4C14-A4T14 and tumor protein p53 (p53) codon 72, either independently or jointly, might be associated with the risk of cervical cancer. Methods: The genotypes of p73 G4C14-A4T14 and p53 codon 72 polymorphisms of peripheral blood DNA from 190 cervical cancer patients and 210 controls were investigated using polymerase chain reaction with confronting two-pair primers and polymerase chain reaction-restriction fragment length polymorphism, respectively. Results: The frequency of p73 G4C14-A4T14 AT/AT (P = 0.013) or p53 codon 72 GG (P = 0.026) genotype was associated with an increased risk of cervical cancer by comparing with the p73 G4C14-A4T14 GC/GC or p53 codon 72 CC genotype, respectively. In addition, the interaction between the p73 G4C14-A4T14 and p53 codon 72 polymorphisms increased the risk of cervical cancer in a multiply manner, with the odds ratio being 3.692 (95% confidence interval =2.106-6.473) for subjects carrying both p73 G4C14-A4T14 GC/AT+AT/AT and p53 codon 72 GG genotypes. Conclusion: These results suggest that there is a statistical difference between p73 and p53 gene polymorphism and the risk of cervical cancer in Chinese women, and there is a potential gene-gene interaction in the incidence of cervical cancer.

Correlation analysis between P73 gene G4C14-to-A4T14 polymorphism and lung cancer risk in Guangdong population / 公共卫生与预防医学

Objective To analyze the correlation between P73 gene G4C14-to-A4T14 double nucleotide polymorphism and the risk of lung cancer in Guangdong population. Methods Genotype analysis of P73 gene polymorphism in peripheral blood of 642 patients with lung cancers (including 450 NSCLC patients and 192 SCLC patients) and 354 normal controls was performed with HRM method (high-resolution fusion curve). Results HRM genotyping results showed that the distribution of P73 genotypes in 450 NSCLC patients was as follows: GC/GC 280 (62.3%), GC/AT 155 (34.4%), and AT/AT 15 (3.3%). P73 genotypes in 192 SCLC patients were 118 GC/GC (61.5%), 67 GC/AT (34.9%) and 7 AT/AT (3.6%). The P73 genotypes of 354 normal controls were 192 GC/GC (53.1%), 136 GC/AT (38.5%), and 26 AT/AT (8.4%). AT/AT homozygous genotypes significantly reduced the risk of NSCLC (OR=0.393；95% CI:0.037-0.873；P=0.001) and SCLC (OR=0.428；95%CI:0.050-0.880；P<0.001) compared with non-carriers. Conclusion The results of the present study indicated that the polymorphism of P73 G4C14-A4T14 may be a modification factor for the susceptibility of lung cancer in Guangdong province, and the increased GC content in the P73 gene may increase the risk of lung cancer.

Advances in p73-targeting anti-tumor drugs / 中国药理学通报

The transcription factor p73 belongs to the p53 family of tumor suppressors,and can be transcribed into different isoforms with either pro-or anti-apoptotic(TAp73 and △Np73)functions.However,the tumor suppressor activity of TAp73 is inhibited through complex formation with inhibitory proteins(e.g.△Np73,mutant p53,MDM2 and iASPP).Therefore,it is a kind of tumor therapy strategy to reactivate TAp73 through targeting these inhibitors directly or release TAp73 from the complex by targeting their interaction.This review discusses the possible strategies of targeting p73 for its reactivation and the acting mechanism of related compounds.

Study on p73 gene polymorphism and genetic susceptibility to hepatocellular cancer / 中国综合临床

Objective To evaluate the potential role of the separately p73 gene polymorphism on hepatocellular carcinoma(HCC) susceptibility.Methods A hospital-based case-control study was conducted in 100 cases HCC patients and 100 cases age,sex-matched cancer-free controls in the same region.The matrix-assisted laser desorption ionization time-of-flight mass spectrometry and DNA sequencing methods were used to analyze polymorphisms of p73 genetic polymorphisms (G4C14-A4T14).Using χ2 test to exam the differences of genotype between the HCC group and control group,logistic regression was used to analysis odds ratio(Oddsratios,OR) and 95%CI(Confidence Intervals,CI),adjusted for age and sex,analysis the association between SNPs of P73 polymorphisms and HCC.All the results were analyzed by SPSS 18.0.Results (1)The differences of age(χ2=0.185,P=0.667),gender(χ2=0.026,P=0.873),drinking status(χ2=0.427,P=0.514),and family history (χ2=0.058,P=0.809)of cancer composition between HCC group and control group were not statistically significant.(2)There were CC,CT and TT three genotypes in p73 rs1801173 C/T.The frequencies of CC,CT and TT genotypes of P73 C/T in controls and HCC cases were 65.0%,28.2%,6.8 % and 62.2%,31.1%,6.7%,respectively,and there was no significant difference between the two groups(χ2=0.326,P=0.568).(3)When stratifying by age,gender,smoking status,alcohol consumption,HBV carrier status and family history of cancer we found that the variant genotypes of GC/AT + AT/AT in P73 was associated with a significantly increased risk of HCC among HbsAg-positive individuals(χ2=3.916,P=0.048) and female(χ2=6.545,P=0.01),and there were no significant correlation with age,smoking,alcohol consumption,family history of cancer.Conclusion (1)p73 G4C14-to-A4T14 dinucleotide polymorphism may play a role in the development of chronic HBV-infected HCC in the Chinese population.(2)p73 G4C14-to-A4T14 dinucleotide polymorphism may play a role in the development of chronic HCC in female of Chinese population.

Expressions and clinical signifcances of matrix metalloproteinase-13 and p73 in gastric adenocarcinoma / 国际肿瘤学杂志

Objective To study the expressions of matrix metalloproteinase-1 3 (MMP-1 3)and p73 in gastric adenocarcinoma,and to explore the associations of the expressions of MMP-1 3 and p73 with the clinico-pathological features,and to evaluate their clinical significances for the prognosis of gastric adenocarcinoma metastasis.Methods The immunohistochemistry SP methods was used to evaluate the expressions of MMP-1 3 and p73 in 1 43 cases of gastric adenocarcinoma and 55 normal tissues adjacent to carcinoma,and their associa-tions to the clinicopathologic features were analyzed.Results The expression of MMP-1 3 in gastric adenocarci-noma was significantly higher than that in adjacent tissues of cancer (67.1 3% vs 1 6.35%),with a significant difference (χ2 =41 .1 0,P =0.000).The expression of p73 in gastric adenocarcinoma was significantly higher than that in adjacent tissues of cancer (58.74% vs 1 2.73%),with a significant difference (χ2 =33.86,P =0.000).In the gastric adenocarcinoma,the expression of MMP-1 3 was associated with peripheral lymph node metastasis (χ2 =1 1 .835,P =0.001 ),depth of invasion (χ2 =5.1 77,P =0.032)and TNM stage (χ2 =1 1 .1 07,P =0.001 ),but it was not correlated with the ages of patients (χ2 =0.1 1 3,P =0.853),tumor size (χ2 =0.338,P =0.591 )and tumor differentiation level (χ2 =3.628,P =0.072).In the gastric adenocarci-noma,the expression of p73 was associated with peripheral lymph node metastasis (χ2 =1 1 .440,P =0.001 ), tumor differentiation level (χ2 =5.407,P =0.025)and TNMstage (χ2 =9.497,P =0.003),but it was not correlated with the ages of patients (χ2 =1 .567,P =0.222),tumor size (χ2 =0.841 ,P =0.392)and depth of invasion (χ2 =0.554,P =0.498).The expression of MMP-1 3 was positively correlated with the expression of p73 in gastric adenocarcinoma group (r =0.684,P =0.000).Conclusion Both MMP-1 3 and p73 may participate in the development of gastric adenocarcinoma,which can be used as an important index for the eval-uation of invasiveness and metastasis in gastric adenocarcinoma.

Correlation between polymorphisms at position 4 and 14 in exon 2 of the p73 gene and susceptibility to human papillomavirus infection / 中华皮肤科杂志

Objective To analyze the correlation between polymorphisms at position 4 and 14 in exon 2 of the p73 gene and susceptibility to human papillomavirus (HPV) infection.Methods Tissue specimens were obtained from the lesions of 83 patients with condyloma acuminatum and 11 patients with bowenoid papulosis,and blood samples from all the patients as well as 150 health checkup examinees with high risk for sexually transmitted diseases (STDs) at STD clinics (negative control group).PCR was performed to detect HPV DNA in lesional tissue specimens,followed by direct sequencing and nucleotide alignment using the BLAST program for the determination of HPV genotypes.To assess polymorphisms at position 4 and 14 in exon 2 of the p73 gene,DNA was extracted from all the blood samples,and the p73 gene was amplified by PCR with the primer shP73 followed by gene sequencing.The association between the polymorphisms and susceptibility to HPV infection was analyzed.Results Of the 83 tissue specimens from patients with condyloma acuminatum,42.2％ (35/83) were positive for HPV 6,and 41.0％ (34/83) for HPV 11.Among the 11 tisssue specimens from bowenoid papulosis lesions,5 were positive for HPV 16,and 3 for HPV 6.The p73 gene was successfully amplified and sequenced from all the patients with condyloma acuminatum or bowenoid papulosis as well as from 132 out of 150 health checkup examinees.There were three genotypes at position 4 and 14 in exon 2 of the p73 gene,including A4T14/G4C14,A4T14/A4T14,G4C14/G4C14,of which,A4T14/A4T14 was associated with a higher risk for condyloma acuminatum (OR 4.89,95％ CI 1.50-15.91) as well as bowenoid papulosis (OR 7.11,95％ CI 1.144-44.20),and G4C14/G4C14 with a lower risk for bowenoid papulosis (OR 0.16,95％ CI0.04-0.65),in patients with HPV infection.Conclusions The A4T14 allele in exon 2 of the p73 gene increases the risk for bowenoid papulosis and condyloma acuminatum,but no significant correlation is found between the susceptibility to high-or low-risk HPV infection and polymorphisms at the two positions in the p73 gene.

Clinical significance of expression of p73 gene and its protein in nasopharyngeal carcinoma / 肿瘤研究与临床

Objective To investigate the expression of p73 gene and its protein and their relation with clinicopathologic features in nasopharyngeal carcinoma (NPC) tissues.Methods Expression of p73 mRNA and protein in 52 NPC and 25 normal nasopharyngeal tissues was detected by real-time fluorescent quantitative PCR and immunohistochemistry.Results Expression of p73 mRNA and protein was significantly higher in NPC than that in normal nasopharyngeal tissues (mRNA:73.1％ vs 24.0 ％,protein:71.2 ％ vs 36.0 ％),there were significant statistical differences between the two groups (P ＜ 0.05),and their expression was closely related to tumor invasion depth,degree of differentiation and clinical stage (P ＜ 0.05).Expression of p73 gene and protein was not closely related to age and gender (P ＞ 0.05).Conclusion Detection expression of p73 mRNA and its protein can be helpful in the diagnosis and prognostic evaluation in NPC.

A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells

MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27KIP1 protein and p21CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21CIP1 , p16INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.

Polymorphism at P21 codon 31 and dinucleotide polymorphism of P73 gene and susceptibility to bladder cancer in individuals from North India.

BACKGROUND AND AIM: p73, a novel P53 homolog and plays an important role in modulating cell cycle control, apoptosis and cell growth while P21, functions to negatively control the cell cycle. P53 up regulates p21 expression in response to deoxyribonucleic acid damage leading to cell cycle arrest at G1 checkpoint. In the present study, we are targeting p21 codon 31 and p73 gene variants of G4C14‑to‑A4T14 (Exon 2) polymorphism for bladder cancer (BC) risk in North Indians. MATERIALS AND METHODS: The above gene variants of P21 and P73 were assessed in the case‑control study comprising of 200 BC cases and 200 healthy controls of the same age, gender and similar ethnicity. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method and PCR‑based confronting two‑pair primers (PCR with CTPP). RESULTS: The variant genotype of p73Exon 2 polymorphism showed significant risk for BC (p = 0.014). While combining with heterozygous genotype, variant genotype of p73Exon2 showed a significant association with BC risk (p = 0.010). While in case of p21 codon31 showed no significant association for BC risk at genotypic level. Significant association between p73Exon2 polymorphism and smoking was observed for BC risk. Furthermore, gene combination analysis revealed that AT/AT‑Ser/Ser is associated with risk for BC. Variant genotype of P73Exon2 was associated with reduced risk of recurrence (p = 0.039) in superficial BC patients receiving Bacillus Calmette‑Guerin treatment thus showing least survival (log rank = 0.029). CONCLUSION: Our study provided evidence that the p73 G4C14 > A4T14 (Exon2) polymorphisms were associated with higher risk of BC in North Indian population.

Influence of triptolide on P53/P73 gene methylation and inhibition effect against proliferation of breast carcinoma MCF-7 cells / 第二军医大学学报

Objective To study the effect of triptolide (TP) on the proliferation of breast carcinoma cell line MCF-7 and its association with P53/P73 gene expression and methylation. Methods MCF-7 cells were treated with different concentrations of TP (10 ng/ml, 20 ng/ml, and 40 ng/ml), and the proliferation of MCF-7 cells was measured by MTT method. The expressions of methyltransferase DNMT1, DNMT3a and DNMT3b mRNA were measured by RT-PCR in MCF-7 cells, P53/P73 gene methylation was analyzed by methylation specific PCR, and the protein expression of p53/P73 in MCF-7 cells was examined by Western blotting assay. Results TP inhibited the proliferation of MCF-7 cells in a dose-dependent manner (P< 0. 05, P<0. 01), with the inhibitory rate being (70. 1 ± 3. 52)% at 40 ng/ml TP, and the IC50 of TP was 20 ng/ml. TP significantly inhibited DNMT1, DNMT3a, and DNMT3b mRNA expression in MCF-7 cells (P<0. 05, P<0. 01), and it also significantly inhibited methylation of P53 promoter region. TP increased P53 gene expression at 20 ng/ml and the increase was significant at 40 ng/ml (P<0. 01). TP reversed the hypermethylation of P73 gene in MCF-7 cells; it also significantly increased P73 mRNA expression at 10 ng/ml (P<0. 05), and the increase was in a dose-dependent manner. Western blotting analysis showed that TP (20 ng/ml) increased the protein expression of P53 and P73 in MCF-7 cells. Conclusion TP can promote the expression of P53 and P73 genes through inhibiting methyltransferase-dependent gene methylation, and further inhibit the proliferation of MCF-7 cells.

p73 activation is involved in regulation of Ara-C-induced apoptosis in human lung adenocarcinoma cells / 解剖学报

Objective To study the apoptosis pathway of human lung adenocarcinoma cell line A549 induced by 1-β-D-arabinofuranosylcytosine (Ara-C) in vitro. Methods A549 cells were incubated with Ara-C for 72hours in vitro. Biological changes of apoptotic cells were studied by TUNEL staining. Morphological changes of the A549 cells treated with Ara-C were observed by transmission electron microscope. The expressions of p53 and p73 were investigated by Western blotting. Results 1.Apoptotic rates of A549 cells exposure to Ara-C studied by TUNEL staining were higher than that of the control (P＜0.01). 2.Apoptosis body was apparently observed by transmission electron microscope. 3.Endogenous p73 but not p53 was induced and activated in dose-dependent manner upon Ara-C treatment by Western blotting.Conclusion Ara-C can effectively induce apoptosis of A549 cells. DNA damage-induced apoptosis of A549 cells treated by Ara-C is independent of functional p53.Up-regulation of p73 may play an important role that enhances the sensitivity of A549 cells to Ara-C and be partly responsible for p53-independent apoptosis.

Cloning and sequencing of a DNA fragment encoding N37 apoptotic peptide derived from p53 / 药物分析学报

Objective It was reported that p53 apoptotic peptide (N37) could inhibit p73 gene through being bound with iASPP, which could induce tumor cell apoptosis. To further explore the function of N37, we constructed the cloning plasmid of DNA fragment encoding p53 (N37) apoptotic peptide by using DNA synthesis and molecular biology methods. Methods According to human p53 sequence from the GenBank database, the primer of p53(N37) gene was designed using Primer V7.0 software. The DNA fragment encoding p53 (N37) apoptotic peptide was amplified by using self-complementation polymerase chain reaction (PCR) method and cloned into the pGEM-T Easy vector. The constructed plasmid was confirmed by endonuclease analysis and sequencing. Results The insertion of objective DNA fragment was confirmed by plasmid DNA enzyme spectrum analysis, p53 (N37) gene was successfully synthesized chemically in vitro. The sequencing result of positive clone was completely identical to the human p53(N37) sequence in GenBank using BLAST software (http://www. ncbi. him. nih. gov/cgi-bin /BLASTn). Conclusion The cloning of DNA fragment encoding p53(N37) apoptotic peptide was constructed by using DNA synthesis and pGEM-T Easy cloning methods. With the constructed plasmid, we could further investigate the function of N37 peptide.

Cloning and sequencing of a DNA fragment encoding N37 apoptotic peptide derived from p53 / 西安交通大学学报·英文版

Objective: It was reported that p53 apoptotic peptide (N37) could inhibit p73 gene through being bound with iASPP, which could induce tumor cell apoptosis. To further explore the function of N37, we constructed the cloning plasmid of DNA fragment encoding p53 (N37) apoptotic peptide by using DNA synthesis and molecular biology methods. Methods: According to human p53 sequence from the GenBank database, the primer of p53 (N37) gene was designed using Primer V7.0 software. The DNA fragment encoding p53 (N37) apoptotic peptide was amplified by using self-complementation polymerase chain reaction (PCR) method and cloned into the pGEM-T Easy vector. The constructed plasmid was confirmed by endonuclease analysis and sequencing. Results: The insertion of objective DNA fragment was confirmed by plasmid DNA enzyme spectrum analysis. p53 (N37) gene was successfully synthesized chemically in vitro. The sequencing result of positive clone was completely identical to the human p53 (N37) sequence in GenBank using BLAST software (http://www.ncbi.nim.nih.gov/cgi-bin/ BLASTn). Conclusion: The cloning of DNA fragment encoding p53 (N37) apoptotic peptide was constructed by using DNA synthesis and pGEM-T Easy cloning methods. With the constructed plasmid, we could further investigate the function of N37 peptide.

p73:a tumor suppressor gene in human non-small cell lung cancer cell lines / 中国病理生理杂志

AIM,To verify whether p73;a homologue of p53,which supposed]y acts as a tumor suppressor gene in neuroblastoma,might also be a tumor suppressor in non-small cell lung cancer.METHODS:The allelic expres-sion of p73 in the six non-small cell lung cancer cell lines was studied by Sty I polymorphism analysis.The P73 gene ex.pressions in these six cell lines were examined by reverse transcription-PCR,the expressions of P73 protein in the five cell lines inducing tumor8 were also determined by immunohistochemistry.RESULTS:Homozygous allelic expression was dem.onstrated in all six cell lines and the GC/GC genotype Was the predominant type.Complete loss of the p73 expression both at mRNA and the protein level was revealed.CONCLUSION:Taken together,our data suggest that p73 might play a role as a tumor suppressor gene in human non-small cell lung cancer cell lines.

Expression of p73 in Non-small Cell Lung Carcinomas

BACKGROUND: The p73 is a recently identified homologue of the tumor suppressor gene, p53, and it has been found to induce apoptosis and inhibit cell proliferation. However, its role in the development of tumors is unclear. This study examined the expression of p73 in patients with non-small cell lung carcinomas (NSCLCs) to determine its clinical significance and association with the expressions of p53, pRb, and mdm2. METHODS: A total of 183 NSCLCs were analyzed immunohistochemically using a tissue microarray. RESULTS: The p73 protein was expressed in the cell nuclei in 156 (85.2%) out of the 183 cases. There was no correlation between the p73 expression and the clinicopathological variables. However, there was a correlation between the p73 expression and the mdm2 and pRb expressions. Multivariate Cox survival analysis identified tumor size and lymph node metastasis to be independent prognostic factors, but the p73 expression was not found to be associated with the patients' survival. CONCLUSIONS: p73 is commonly expressed in NSCLC and it might, in conjunction with pRb and mdm2, be involved in the development of these tumors.

Elevated Expression of p73 and Its Relation to VEGF and TSP-1 Production in Cervical Carcinoma / 대한산부인과학회지

OBJECTIVE: Measure the over-expression of p73 and analyze as the prognostic as well as angiogenic factor of cervical cancer by comparing the degree of expression of VEGF and TSP-1 by RT-PCR. METHODS: 7 normal and 37 cervical cancer specimens were put through RT-PCR and the expression of p73, VEGF and TSP-1 were measured. After immunohistochemical staining, the number of microvessels was counted. With the level of expression, investigated the relationship with the clinicopathological characteristics and the number of microvessels. RESULTS: 57% of cancer tissues showed abnormally high levels of p73 mRNA. In quantitative genomic DNA PCR, the p73 was over-expressed in the transcription level. Through allotyping with Sty I polymorphism, the over-expression of p73 was due to the transcription activity of the silent allele. In RT-PCR-SSCP analysis of over-expressed specimens, sequence alterations was not seen. In 73%, VEGF was over-expressed while TSP-1 was under-expressed in 35%. There was no association between the number of microvessels with the over-expression of p73 and VEGF, but inversely associated with the under-expression of TSP-1. There was no correlation between the over-expression of p73 and the clinicopathological characteristics. The over-expression of p73 coincided 80% with the over-expression of VEGF, and 40% with the under-expression of TSP-1. CONCLUSION: These data support the expression of p73 was increased in cervical cancer tissues and was associated with the over-expression of the VEGF but not associated with the under-expression of TSP-1. The biological and clinical significance of the over-expression of p73 should be studied further in the future.

p63 and p73 in Tumor Suppression and Promotion / Journal of the Korean Cancer Association, 대한암학회지

The recent discovery of two genes, termed p63 and p73, encoding transcription factors highly homologous to p53 presents unexpected challenges and opportunities for the understanding and treatment of cancers. The questions raised are many but center on determining whether these new genes possess novel tumor suppressor functions, cooperate with p53, or impart oncogenic effects. At present there is considerable discord in the field concerning these concepts with some favoring a tumor suppressor role for the p53 family members and others an oncogenic influence. In support of a tumor suppressor role is the ability of p73 and p63 isoforms to transactivate p53 target genes and the large body of work linking p73, and to some extent p63, in apoptotic events in response to cellular stresses generally considered the purview of p53. More recently, p73 has been implicated in cell death following T cell activation, the response of cancers to chemotherapy, and finally, along with p63, to the function of p53 itself. Opposing this view is the fact that the p73 and p63 genes are rarely mutated in cancers and the stark absence of tumors in the p73 null mouse. Moreover, the high expression of dominant negative (dn) versions of the p73 and p63 proteins supports an anti-p53 function and therefore possibly an oncogenic effect. Indeed, the p63 gene is located in a region of chromosome three amplified in squamous cell carcinomas and the number of reports of dn-p63 overexpression in these diseases is increasing. This review will examine both sides of these arguments in an attempt to decipher common themes and to identify opportunities these genes represent for understanding tumorigenesis.

Expression of p53 and p73 Genes in Human Transitional Cell Carcinoma of the Bladder / 대한비뇨기과학회지

PURPOSE: We analyzed the tissue samples of bladder transitional cell carcinoma (TCCa) for both the p53 and p73 gene, and we attempted to elucidate their possible roles in the pathogenesis of bladder TCCa. MATERIALS AND METHODS: After homogenizing 33 samples of bladder TCCa and 3 normal bladder tissues, the genomic DNA was isolated for PCR. The primers used for PCR were exon 5-10 for p53 and exon 8 and 13 for p73. The mutation analysis was performed by an automatic sequencing analyzer. The results were compared to the grade and stage of the bladder cancers. RESULTS: Mutations of p53 and p73 were noted in 18 (54.5%) and 19 samples (57.6%), respectively, out of 33 bladder cancer tissue samples. The frequency of p53 mutation were significantly higher for invasive and high grade cancer (p=0.04). Mutation of p73 show no statistically significant difference according to invasiveness (p=0.224); however, it show a significantly higher incidence in high grade cancer (p=0.026). Simultaneous mutations of p53 and p73 show a significant increase in higher grade cancer (p=0.025) and in the higher cancer stages (p=0.045). Recurrence-free probabilities for patients with superficial bladder cancer were significantly correlated with the p53 and p73 mutation. CONCLUSIONS: Mutation of p73, as well as p53, which is already known as a predictor for the recurrence and progression of bladder cancer, also seems to be related to the pathogenesis and prognostic factors of TCCa of the bladder.

Expression of p73 in Benign and Malignant Epidermal Tumors and in Normal Skins / 中华皮肤科杂志

Objective To investigate the expression of p73 protein in normal skins and lesions of benign and malignant epidermal tumors. Methods By immunohistochemical staining, the expression of p73, p53 and Ki67 was examined in 19 cases of seborrheic keratosis (SK), 16 basal cell carcinoma (BCC), 11 Bowen's disease (BD), 5 squamous cell carcinoma (SCC),as well as in 10 normal skin controls. Results In normal skin, p73 protein was found to distribute in the basal cells of the epidermis, basal cells in the outer root sheath of the hair follicles, and the germinative cells in the sebaceous glands. p73 was expressed strongly in the basal cell-like cells of BCC and SK lesions, and in the atypical cells of BD lesions, but weakly or even negatively in the tumor cells of SCC lesions and the squamous cell-like cells of SK lesions. There was significant difference in the expression of p73 among the SK, BD, BCC and SCC lesions (H=12.71 ,P

The Expression and Significant of P73, P53, P21~(waf1) and PCNA Protein in the Different Diseases of Gastric Mucosa / 中国医师杂志

Objective To investigate the relation between expression of P73 , P53, P21 waf1 ,PCNA protein in the different diseases of gastric mucosa and the malignant transformation of gastric mucosa epithelium and their correlation in gastric carcinoma and the relation to histological type , lymph node metastases, depth of invasion of gastric mucosa ,TNM stage in gastric carcinoma. Methods Immunohistochemical staining(S-P method) was used to detect the expression of P73, P53, P21 waf1 , PCNA protein in 39 cases of gastric carcinoma, 17 cases of chronic atrophic gastritis and 40 cases of chronic inflammatory polyp and a statistical analysis was made according to clinicopathogical data. Results The positive rate of P73 protein expression in gastric carcinoma was remarkably higher than that in chronic inflammatory polyp and that in chronic atrophic gastritis( P 0.05). there was negative correlation between expression of P21 waf1 protein and TNM stage, lymph node metastases( P 0.05). Conclusion Probably high expression of P73 gene is one hot spot gene alteration of gastric carcinoma and expression of P73 protein in gastric carcinoma may play an important role in the course of cancerous development. As one tumor suppressor gene, P73 has its tissular specificity. Cooperative expression of P73 and PCNA,and the correlation of expression to P73 and P53 、P21 waf1 protein could be an important index to judge the malignant transformation and clinicopathological process and prognosis. P21 waf1 may be an early signal of gastric carcinoma or one of indexes to judge prognosis.