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@#[摘 要] 目的：探讨长链非编码RNA（lncRNA）LINC01410对胶质瘤A172细胞增殖、凋亡和替莫唑胺（temozolomide, TMZ）敏感性的影响及其机制。方法: 用qPCR法检测胶质瘤细胞系H4、SHG-44、A172和正常星形胶质细胞HA1800中LINC01410表达水平。将LINC01410 shRNA、shRNA control和miR-205-5p 抑制剂（inhibitor）、inhibitor control转染至A172细胞，MTT法、流式细胞术分别检测400 μmol/L TMZ处理后，转染细胞的增殖活性和凋亡水平，WB法检测细胞中Bax、Bcl-2、cyclin D1、p27的表达。在线生物信息学软件LncBase分析LINC01410的靶基因，双荧光素酶报告基因实验验证LINC01410与miR-205-5p的靶向关系。结果: LINC01410在3种胶质瘤细胞中的表达水平均显著高于正常星形胶质细胞HA1800（均P<0.01），以在A172细胞中的表达水平最高（P<0.01）。转染LINC01410 shRNA和TMZ处理后，A172细胞的增殖能力下降、G1期细胞比例和凋亡率均升高（均P<0.01），细胞中Bax、p27表达水平升高而Bcl-2、cyclin D1表达水平下降（均P<0.01）。双荧光素酶报告基因实验证实LINC01410靶向结合miR-205-5p，下调LINC01410促进miR-205-5p表达。转染miR-205-5p抑制剂可逆转下调LINC01410和TMZ处理对A172细胞增殖、周期和凋亡的影响。结论: 下调lncRNA LINC01410可抑制胶质瘤A172细胞增殖、阻滞细胞周期、诱导细胞凋亡且提高对TMZ敏感性，其发生机制似与LINC01410对miR-205-5p的靶向作用有关。
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Objective:To explore the mechanism of miR-205-5p/E2F1 signal axis in regulating the glioma U251, U87 radiotherapy resistance.Methods:X-ray gradual ascending and intermittent induction method was used to irradiate the glioma U251 cells to establish U251/TR, U87/TR radiation-resistant cell lines. Then, the morphology, migration, invasion and proliferation abilities of cells (U251/TR, U87/TR radiation-resistant cells and U251, U87 radiation-sensitive cells) were analyzed. Luciferase gene detection system and point mutation technique were employed to analyze the mechanism of miR-205-5p and E2F1 gene activity on U251 and U87 radiation-resistant cell lines.Results:Compared with the radiation-sensitive U251 cells, the radiation-resistant cells U251/TR, U87/TR showed increased proliferation activity, enhanced migration and invasion abilities and decreased apoptosis under X-ray irradiation. miR-205-5p mimics transfection could down-regulate the expression of E2F1 factor in U251/TR cells, inhibit cell proliferation, invasion and migration and increase the radiosensitivity of U251/TR cells. miR-205-5p mimics transfection combined with with E2F1 down-regulation exerted anti-tumor effect and decreased cell tolerance by suppressing the Wnt/β-catenin signaling pathway activity.Conclusions:The glioma radiation-resistant cell line U251/TR, U87/TR can be established by X-ray gradual ascending and intermittent induction method. The miR-205-5p/E2F1 signal axis exerts tumor-suppressing effect through the classical Wnt/β-catenin signaling pathway, which can be used as an therapeutic target to increase the radiosensitivity of glioma.
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This study aims to investigate the effect of down-regulation of miR-205-5p by transfection of miR-205-5p inhibitor on the sensitivity of HNE1/DDP cells to cisplatin (DDP) induced apoptosis and explore the underlying mechanism. qRT-PCR was used to detect the expression of miR-205-5p in HNE1 or HNE1/DDP cells. The expression level of miR-205-5p was analyzed after transfecting HNE1/DDP cells with miR-205-5p inhibitor. MTT assay was used to evaluate the inhibitory effect of DDP alone or in combination with miR-205-5p inhibitor on the proliferation of HNE1/DDP or HNE1 cells. Apoptosis of cells treated with miR-205-5p inhibitor alone or in combination with DDP (8 μmol·L-1) was assessed using flow cytometry with PI staining, with the nucleus was counterstained with DAPI staining. The expression of Bax, Bak, Mcl-1, or Bcl-2 was analyzed by Western blot. HNE1/DDP cells showed a high level of expression of miR-205-5p, and the expression of miR-205-5p was significantly decreased by transfection of miR-205-5p inhibitor. Down-regulation of miR-205-5p significantly increased the sensitivity of HNE1/DDP cells to DDP (P<0.05). Transfection of miR-205-5p inhibitor enhanced the sensitivity of HNE1/DDP cells to DDP induced apoptosis. Treatment of HNE1/DDP cells with miR-205-5p inhibitor combined with DDP (8 μmol·L-1) for 24 h resulted in an apoptotic rate of 28.93% ± 2.50%, significantly higher than that treated with miR-205-5p inhibitor (9.83% ± 1.31%) or DDP alone (10.83% ± 1.70%) (P<0.05). DAPI staining showed that HNE1/DDP cell nucleus became significantly condensed and fragmented in miR-205-5p inhibitor combined with DDP group. The combined group up-regulated the expression of Bax and down-regulated the expression of Bcl-2 in HNE1/DDP cells. Therefore, down-regulation of miR-205-5p can enhance the sensitivity of HNE1/DDP cells to cisplatin induced apoptosis, and the mechanism may involve up-regulation of Bax and down-regulation of Bcl-2 expression.
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OBJECTIVE@#To investigate the effect of down-regulation of miR-205-5p on 3-bromopyruvate-induced apoptosis in human nasopharyngeal carcinoma CNE2Z cells.@*METHODS@#Nasopharyngeal carcinoma CNE2Z cells were transfected with miR- 205-5p-mimic or miR-205-5p-inhibitor, treated with 80 μmol/L 3-bromopyruvate alone, or exposed to both of the treatments. The proliferation of the treated cells was examined with MTT assay, and early apoptosis of the cells was detected using a mitochondrial membrane potential detection kit (JC-1). DAPI fluorescence staining was used to detect morphological changes of the cell nuclei and late cell apoptosis; Annexin V-FITC/PI double staining was employed to detect the cell apoptosis rate. Western blotting was used to detect the expressions of Bcl-2, Bax, Mcl-1 and Bak proteins.@*RESULTS@#Exposure to 3-bromopyruvate significantly inhibited the proliferation of CNE2Z cells, and increasing the drug concentration and extending the treatment time produced stronger inhibitory effects. Treatment with 80 μmol/L 3-bromopyruvate for 24, 48 and 72 h resulted in inhibition rates of (45.7±1.21)%, (64.4±2.02)% and (78.3±1.55)% in non-transfected CNE2Z cells, respectively; the inhibition rates were (27.7±1.04)%, (34.8±2.10)% and (44.3±1.57)% in the cells transfected with miR-205-5p-mimic, and were (80.5 ± 0.94)%, (87.9 ± 0.50)% and (93.8 ± 1.16)% in cells transfected with miR-205-5p-inhibitor, respectively. The results of mitochondrial membrane potential detection showed that the relative proportion of red and green fluorescence decreased significantly in miR-205-5p-inhibitor-transfected cells with 3-bromopyruvate treatment. Combined treatment of the cells with 3-bromopyruvate and miR-205-5p-inhibitor transfection obviously increased nuclear fragmentation and nuclear pyknosis and significantly increased cell apoptotic rate as compared with the two treatments alone ( < 0.01), causing also decreased expressions of Bcl-2 and Mcl-1 proteins and increased expressions of Bax and Bak proteins.@*CONCLUSIONS@#Inhibition of miR-205-5p enhances the proapototic effect of 3-bromopyruvate in CNE2Z cells possibly in relation to the down-regulation of Mcl-1 and Bcl-2 and the up-regulation of Bak and Bax proteins.
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Objective@#To investigate the serum levels and clinical significances of microRNA-205 (miR-205) and microRNA-221 (miR-221) in patients with colon cancer.@*Methods@#A total of 172 patients with colon cancer (colon cancer group), 130 patients with benign diseases of colon (benign lesion group) and 70 healthy persons (control group) admitted to Central Hospital of Western Hainan from January 2016 to December 2018 were selected. The serum levels of miR-205 and miR-221 in each group were detected, and their relationships with clinicopathological characteristics of patients with colon cancer were analyzed. The diagnostic values of the serum levels of miR-205 and miR-221 in colon cancer were analyzed by receiver operating characteristic (ROC) curve. Pearson correlation analysis was used to analyze the correlation between the serum levels of miR-205 and miR-221.@*Results@#The serum levels of miR-205 in colon cancer group, benign lesion group and control group were 2.84±0.96, 1.16±0.27 and 1.05±0.23, with a statistically significant diffe-rence (F=10.113, P<0.001). The serum levels of miR-221 in the three groups were 1.95±0.74, 0.37±0.08 and 0.32±0.05, with a statistically significant difference (F=12.416, P<0.001). Further pairwise comparisons found that the serum levels of miR-205 and miR-221 in colon cancer group were significantly higher than those in benign lesion group and control group (all P<0.001). The serum levels of miR-205 and miR-221 in patients with colon cancer were related with TNM stage (t=5.412, P<0.001; t=6.103, P<0.001), degree of tumor differentiation (t=4.573, P=0.028; t=4.805, P=0.013) and with or without lymph node metastasis (t=5.837, P<0.001; t=7.410, P<0.001). ROC curve analysis showed that the optimal cut-off values of the serum levels of miR-205 and miR-221 for the diagnosis of colon cancer were 2.17 and 1.30, respectively. The area under the curve of the two combined diagnostic method for colon cancer was the largest (0.924, 95%CI: 0.865-0.983), with the sensitivity and specificity of 91.3% and 87.4%. The correlation analysis showed that the serum levels of miR-205 and miR-221 were positively correlated in patients with colon cancer (r=0.837, P<0.001).@*Conclusion@#The serum levels of miR-205 and miR-221 are significantly increased in patients with colon cancer, and the two combined detection has a high value for the diagnosis of colon cancer.
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Objective To investigate the serum levels and clinical significances of microRNA-205 (miR-205) and microRNA-221 (miR-221) in patients with colon cancer.Methods A total of 172 patients with colon cancer (colon cancer group),130 patients with benign diseases of colon (benign lesion group) and 70 healthy persons (control group) admitted to Central Hospital of Western Hainan from January 2016 to December 2018 were selected.The serum levels of miR-205 and miR-221 in each group were detected,and their relationships with clinicopathological characteristics of patients with colon cancer were analyzed.The diagnostic values of the serum levels of miR-205 and miR-221 in colon cancer were analyzed by receiver operating characteristic (ROC) curve.Pearson correlation analysis was used to analyze the correlation between the serum levels of miR-205 and miR-221.Results The serum levels of miR-205 in colon cancer group,benign lesion group and control group were 2.84 ± 0.96,1.16 ± 0.27 and 1.05 ± 0.23,with a statistically significant difference (F =10.113,P ＜ 0.001).The serum levels of miR-221 in the three groups were 1.95 ± 0.74,0.37 ± 0.08 and 0.32 ± 0.05,with a statistically significant difference (F =12.416,P ＜ 0.001).Further pairwise comparisons found that the serum levels of miR-205 and miR-221 in colon cancer group were significantly higher than those in benign lesion group and control group (all P ＜ 0.001).The serum levels of miR-205 and miR-221 in patients with colon cancer were related with TNM stage (t =5.412,P ＜0.001;t =6.103,P ＜0.001),degree of tumor differentiation (t =4.573,P =0.028;t =4.805,P =0.013) and with or without lymph node metastasis (t =5.837,P ＜ 0.001;t =7.410,P ＜ 0.001).ROC curve analysis showed that the optimal cut-off values of the serum levels of miR-205 and miR-221 for the diagnosis of colon cancer were 2.17 and 1.30,respectively.The area under the curve of the two combined diagnostic method for colon cancer was the largest (0.924,95％ CI:0.865-0.983),with the sensitivity and specificity of 91.3％ and 87.4％.The correlation analysis showed that the serum levels of miR-205 and miR-221 were positively correlated in patients with colon cancer (r =0.837,P ＜0.001).Conclusion The serum levels of miR-205 and miR-221 are significantly increased in patients with colon cancer,and the two combined detection has a high value for the diagnosis of colon cancer.
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Objective:To investigate the relationship between LncRNA MALAT-1 and miR-205 in non-small cell lung cancer and the mechanism of biological behavior in lung cancer cells.Methods: The expression of LncRNA MALAT-1 in different non-small cell lung cancer was detected by qPCR.The interaction between MALAT-1 and miR-205 was detected by double luciferase reporter gene.Transwell invasion assay and scratch test were used to detect the changes of invasion and migration abilities of lung cancer cells after silencing MALAT-1 and the recovery the abilities after inhibition of miR-205 expression.The tumor volume and quality of lung cancer cells were detected by subcutaneous tumor formation in nude mice after silencing MALAT-1.Results:Compared with other lung cancer cell lines,the expression of MALAT-1 was the highest and the expression level of miR-205 was the lowest in A549 cells.The double luciferase assay confirmed that MALAT-1 could specifically bind to 3′UTR of miR-205,and could regulate the expression and activity of miR-205.Inhibition of MALAT-1 expression could reduce the migration and invasion of lung cancer cells;while inhibiting the expression of miR-205 level,the migration and invasion of lung cancer cells could recovery.The tumor volume and quality of lung cancer cells were reduced after silencing MALAT-1 in subcutaneous tumorigenesis of nude mice.Conclusion: MALAT-1 can regulate the expression of miR-205 and affect the invasion and migration of lung cancer cell line A549.
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As evolutionarily conservative small non-coding regulatory RNAs, microRNAs (miRNAs) are capable of silencing gene expression by translational repression or mRNA degradation through complementary base pairing with the mRNA of target genes. Accumulating evidence indicates that deregulation of miRNAs is often associated with human malignancies because miRNAs can function as oncogenes or tumor suppressors. Among them, miR-205 is significantly underexpressed in breast tumors. Overexpression of miR-205 in breast cancer cells significantly inhibits cell proliferation, invasion and metastasis through repressing the expression of human epidermal growth factor receptor 3 (ERBB3), zinc finger E-box binding homeobox 1 (ZEB1), zinc finger E-box binding homeobox 2 (ZEB2), vascular endothelial growth factor A (VEGFA) and other target genes, which affects therapeutic sensitivity and prognosis of breast cancer patients. This article reviews the role and regulation of miR-205 in breast cancer, the value of miR-205 in clinical application and miR-205 related research progress, which is expected to provide new strategy and therapeutic target for breast cancer diagnosis, treatment and prognosis.
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As evolutionarily conservative small non-coding regulatory RNAs, microRNAs (miRNAs) are capable of silencing gene expression by translational repression or mRNA degradation through complementary base pairing with the mRNA of target genes. Accumulating evidence indicates that deregulation of miRNAs is often associated with human malignancies because miRNAs can function as oncogenes or tumor suppressors. Among them, miR-205 is significantly underexpressed in breast tumors. Overexpression of miR-205 in breast cancer cells significantly inhibits cell proliferation, invasion and metastasis through repressing the expression of human epidermal growth factor receptor 3 (ERBB3), zinc finger E-box binding homeobox 1 (ZEB1), zinc finger E-box binding homeobox 2 (ZEB2), vascular endothelial growth factor A (VEGFA) and other target genes, which affects therapeutic sensitivity and prognosis of breast cancer patients. This article reviews the role and regulation of miR-205 in breast cancer, the value of miR-205 in clinical application and miR-205 related research progress, which is expected to provide new strategy and therapeutic target for breast cancer diagnosis, treatment and prognosis.
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Traditional research ideas of miRNA-target gene-biological function have ignored the contact between the target genes and signaling pathways involved , making the integrity and relevance of miRNA regulatory mechanisms not be fully elucidated .Integrated with systematic and relevant way of thinking , summarization and analysis for the luciferase reporter assay validated miR-205 target genes and their related signaling pathways will pave the way for new research area for miR-205 , and , it will be helpful for breaking through the status quo and exploring the novel research areas for miRNA .
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Objective To determine the expressions of miR-200a, miR-141, miR-205 and miR-34a in epithelial ovarian cancer (EOC) samples and to explore their clinical significance. Methods According to FIGO staging, 44 EOC pa?tients were divided into two groups:early FIGO stage (stageⅠ-Ⅱ, n=15) and late FIGO stage (stageⅢ-Ⅳ, n=29). Expres?sions of 4 miRNAs were detected by real time quantitative PCR, and were compared between two groups. The correlation of 4 miRNAs was calculated. EOC patients were divided into high miRNA expression group and low expression group according to the median value of miRNAs expression. Kaplan-Meier survival analysis and Cox multivariate analysis were used to com?pare the age, FIGO state, tumor residual after operation and post-operative chemotherapy of ovarian cancer between two groups. Results The expression of miR-141 was elevated in stagesⅢandⅣcompared with that of stagesⅠand Ⅱ(P=0.036). There was a positive correlation between expression of miR-141, miR-200a and miR-205, but a negative correlation with miR-34a (P<0.05). There was a positive correlation between miR-200a and miR-205 (P<0.05). Lower miR-200a ex?pression was associated with shorter progress free survival in ovarian cancer analyzed by log-rank test ( P=0.035). The sur?vival rate was significantly higher in FIGO stages ⅠandⅡthan that of FIGO stagesⅢandⅣ(P<0.05). Cox regression analysis revealed that miR-200a, FIGO stage and age were influential factors of overall survival time and progress-free sur?vival time of ovarian cancer, while miR-141, miR-205, miR-34a and tumor residual after operation and post-operative che?motherapy were not influential factors. Conclusion The expression of miR-200a is closely correlated with the progress and prognosis of ovarian cancer and may be used as an independent indicator for ovarian cancer prognosis.
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BACKGROUND: The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. miR-205 was reported to be upregulated in laryngeal squamous cell carcinoma (LSCC) tissues, however, the mechanisms by which miR-205 functions as a regulator of LSCC are largely unknown. RESULTS: In this study, Real-time qPCR and Western blot assay showed that expression of miR-205 was upregulated and expression of cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) was downregulated in LSCC tissues. The expression levels of miR-205 were negatively related to those of CDK2AP1 in LSCC tissues and cell lines. Moreover, we found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the CDK2AP1 expression in LSCC cells. 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyl-tetrazolium bromide assays and transwell invasion assay were performed to test the proliferation and invasion of LSCC cells. Gelatin zymography was used to detect the activity of MMP2 and MMP9. CDK2AP1, c-Myc and CyclinD1 expression in cells was assessed with Western blotting. We found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the expression of CDK2AP1 in LSCC cells. In addition, miR-205 significantly induced cell proliferation and invasion by suppressing CDK2AP1 expression. Consistent with miR-205 inhibitors, overexpressed CDK2AP1 suppressed the activity of MMP2 and MMP9 and c-Myc and CyclinD1 expression in LSCC cells. CONCLUSION: These findings help us to better elucidate the molecular mechanisms of LSCC progression and provide a new theoretical basis to further investigate miR-205 as a potential biomarker and a promising approach for LSCC treatment.
Subject(s)
Humans , Suppression, Genetic/genetics , Carcinoma, Squamous Cell/pathology , Laryngeal Neoplasms/pathology , Tumor Suppressor Proteins/genetics , MicroRNAs/genetics , Cell Proliferation/genetics , Carcinoma, Squamous Cell/enzymology , Biomarkers, Tumor , Down-Regulation , Gene Expression Regulation, Neoplastic , Blotting, Western , Genes, myc/genetics , Cyclin D1/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Tumor Suppressor Proteins/metabolism , MicroRNAs/metabolism , Hep G2 Cells , Primary Cell Culture , Real-Time Polymerase Chain Reaction , Neoplasm Invasiveness/geneticsABSTRACT
Objective To detect the expression levels of the miR-205 in lung cancer tissue and A549 cells and its targeted gene YES1 using qRT-PCR and dual fluorescence protein repoter assay system,and to explore the possible mechanism of miR-205 to inhibit the proliferation of lung cancer A549 cells.Methods The expression levels of miR-205 in 10 cases of lung cancer tissue and adjacent normal lung tissue were detected with qRT-PCR.The cell growth curve and colony formation assay were used to determine the proliferation rate of A549 cells after transfected by miR-205 mimics and control mimics.The sequences of YES1 3′UTR (untranslated region)and mutation target sites of YES1 3′UTR were inserted into the plasmid which expressed green fluorescence protein (pcDNA3/EGFP) respectively to construct the green fluorescence protein plasmids of YES1-3′UTR and mut-YES1-3′UTR. There were six groups in the study:YES1-3′UTR, YES1-3′UTR and miR-205 mimics, YES1-3′UTR and control mimics,mut-YES1-3′UTR, mut-YES1-3′UTR and miR-205 mimics, mut-YES1-3′UTR and control mimics;after the plasmids expressed red fluorescent protein (pDsRed2-N1 )were cotransfected into A549 cells,the extracted protein was detected with fluorescence spectrophotometer.Results Compared with adjacent normal lung tissue,the expression levels of miR-205 in lung cancer tissue and A549 cells were decreased (P<0.05 );the proliferation rate of A549 cells in miR-205 mimics group was lower than that in control mimics group (P<0.05). The fluorescence protein expression level in YES1-3′UTR and miR-205 mimics co-transfected group was lower than that in YES1-3′UTR and control mimics co-transfected group, the difference was statistically significant (P<0.01).The number of cell colony formation of A549 cells in highly expressed YES1 group was higher than that in cell control group (P<0.05).Conclusion MiR-205 may inhibit the proliferation of A549 cells through regulating of the expression of YES1 directly.miR-205 and YES1 are potential therapeutic targets for the biological treatment of tumor.
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Os tumores de mama são caracterizados pela sua alta heterogeneidade. O câncer de mama é uma doença complexa, que possui o seu desenvolvimento fortemente influenciado por fatores ambientais, combinada a uma progressiva acumulação de mutações genéticas e desregulação epigenética de vias críticas. Alterações nos padrões de expressão gênica podem ser resultado de uma desregulação no controle de eventos epigenéticos, assim como, na regulação pós-transcricional pelo mecanismo de RNA de interferência endógeno via microRNA (miRNA). Estes eventos são capazes de levar à iniciação, à promoção e à manutenção da carcinogênese, como também ter implicações no desenvolvimento da resistência à terapia Os miRNAs formam uma classe de RNAs não codificantes, que durante os últimos anos surgiram como um dos principais reguladores da expressão gênica, através da sua capacidade de regular negativamente a atividade de RNAs mensageiros (RNAms) portadores de uma seqüencia parcialmente complementar. A importância da regulação mediada por miRNAs foi observada pela capacidade destas moléculas em regular uma vasta gama de processos biológicos incluindo a proliferação celular, diferenciação e a apoptose. Para avaliar a expressão de miRNAs durante a progressão tumoral, utilizamos como modelo experimental a série 21T que compreende 5 linhagens celulares originárias da mesma paciente diagnosticada com um tumor primário de mama do tipo ErbB2 e uma posterior metástase pulmonar. Essa série é composta pela linhagem obtida a partir do tecido normal 16N, pelas linhagens correspondentes ao carcinoma primário 21PT e 21NT e pelas linhagens obtidas um ano após o diagnóstico inicial, a partir da efusão pleural no sítio metastatico 21MT1 e 21MT2. O miRNAoma da série 21T revelou uma redução significativa nos níveis de miR-205 e nos níveis da proteina e-caderina e um enriquecimento do fator pró-metastático ZEB-1 nas células 21MT...
Breast tumors are characterized by their high heterogeneity. It is a complex disease, which has its development strongly influenced by environmental factors, combined with a progressive accumulation of genetic mutations and epigenetic dysregulation of critical pathways. Changes in gene expression patterns may be a result of a deregulation in epigenetic events as well as in post-transcriptional regulation driven by RNA interference endogenously represented by microRNA (miRNA) these mechanisms are capable to promote the initiation, maintenance and progression of carcinogenesis; they are also implicated on the development of therapy resistance. miRNAs form a class of non-coding RNAs which have emerged in recent years as one of the major regulators of gene expression through its capacity to silence messenger RNAs (mRNAs) containing a partially complementary sequence. The importance of regulation mediated by miRNAs was observed on their ability to regulate a wide range of biological processes including cell proliferation, differentiation and apoptosis.To gain insights into the mechanisms involved in breast cancer initiation and progression conducted a miRNA global expression on 21T series that are an in vitro model of breast cancer progression comprising cell lines derived from the same patient which include a normal epithelia (16N), primary in situ ductal carcinoma (21PT and 21NT) and cells derived from pleural effusion of lung metastasis (21MT-1 and 21MT-2)...