Effect of the exogenous fragile histidine triad(FHIT)gene on the proliferation and apoptosis of cutaneous carcinoma cell line A431 / 基础医学与临床

Objective To investigate the effect of the exogenous fragile hisdidine triad(FHIT) gene on the proliferation and the apoptosis of cutaneous carcinoma cell line A431,and to explore the mechanism of tumor suppression by the FHIT gene.Methods The plasmids pcDNA3-FHIT and pcDNA3-vector were transfected into the cutaneous carcinoma cell line A431 without FHIT gene expression,and then the transfected cells were screened by G418 and the expression of FHIT was determined by the immunocytochemical staining technique.The effect of FHIT on the growth characteristics of cutaneous carcinoma cell line A431 was observed by MTT,colony forming test and flow cytometry.Results Stable FHIT gene expressing A431 cells were produced,the proliferation activity and colony forming capability of A431FHIT were suppressed,whereas the apoptosis was increased.All these differences between A431-FHIT cells and the two control groups of cutaneous carcinoma cells had statistical significance.Conclusion Transfecting the exogenous FHIT gene into cutaneous carcinoma cells line A431can suppress the proliferation of tumor cells,and can also induce apoptosis and cell cycle arrest.

Mechanism of FHIT-Induced Apoptosis in Lung Cancer Cell Lines / 결핵

BACKGROUND: The FHIT (fragile histidine triad) gene is a frequent target of deletions associated with abnormal RNA and protein expression in lung cancer. Previous studies have shown FHIT gene transfer into lung cancer cell line lacking FHIT protein expression resulted in inhibition of tumor cell growth attributable to the induction of apoptosis and reversion of tumorigenecity. However, the mechanism of the tumor suppressor activity of the FHIT gene and the cellular pathways associated with its function are not completely understood. METHODS: To gain insight into the biological function of FHIT, we compared the NCI-H358 cell line with its stable FHIT transfectants after treatment with cisplatin or paclitaxel. We investigated the effects of FHIT gene expression on cell proliferation, apoptosis, and activation of caspase system and Bcl-2 family. The induction of apoptosis was evaluated by using DAPI staining and flow cytometry. Activation of caspases and Bcl-2 members was evaluated by Western blot analysis. RESULTS: A significantly increased cell death was observed in FHIT transfectants after cisplatin or paclitaxel treatment and this was attributable to the induction of apoptosis. Remarkable changes in caspases and Bcl-2 family were observed in the transfected cells as compared with the control cells after treatment with paclitaxel. Activation of caspase-3 and caspase-7 was markedly increased in cells expressing FHIT. Expression level of Bcl-2 and Bcl-xL protein was significantly decreased and that of Bax and Bad protein was significantly increased in the transfected cells. CONCLUSION: FHIT gene delivery into lung cancer cells results in enhanced apoptosis induced by treatment with cisplatin or paclitaxel. The data suggest that apoptosis in FHIT-expressing cells could be related to activation of caspase pathway and Bcl-2 family.

FHIT alteration in human esophageal, gastric and colorectal carcinomas / 中华消化杂志

Objective To investigate the status of fragile histidine triad (FHIT) gene in human esophageal, gastric and colorectal carcinomas. Methods Ninety six samples of digestive tract cancer (including 21 esophageal carcinomas, 43 gastric carcinomas and 32 colorectal carcinomas) tissues and their adjacent non carcinoma tissues and 18 samples of normal tissue were examined by nested RT PCR for FHIT gene alteration. Results Aberrant transcripts were observed in 33.3% esophageal cancers, 51.7% gastric cancers and 31.3% colorectal cancers. In the adjacent esophageal,gastric and colorectal non carcinoma tissues the rate of aberrant transcripts were 4.8%,20.9% and 9.4%, respectively ( P

The expression of FHIT protein and p21 protein in vulvar condyloma acuminatum and vulvar intraepithelial neoplasia / 重庆医科大学学报

Objective:To probe the expression of Fragile histidine triad(FHIT)and p21 protein in Vulvar Condyloma acuminatum(VCA) and vulvar intraepithelial neoplasia(VIN).Methods:Immunohistochemistry was used to detect FHIT and p21 expression in 51 cases of VCA,39 cases of VIN and 20 cases of normal vulvar epithelium.Results:The positive rate of FHIT in VCA and VINⅠ～Ⅱ、VINⅢwas obviously lower than which in normal tissue(P=0.000 1);there was no statistic significance in the positive rate of FHIT expression between VINⅢand VCA(P=0.592);the positive rate of p21 in normal vulva,VIN and VCA has statistic significance;there was no statistic significance in the positive rate of p21 expression between VIN and VCA(P=0.793).Conclusion:(1)FHIT and p21 expression are associated with the development and progression of VCA and VIN(.2)The abnormality of FHIT gene is a early event in the development and progression of vulvar cancer.

Fragile histidine triad transcription abnormalities and human papillomavirus16 infection in human cervical carcinoma / 西安交通大学学报(医学版)

Objective To evaluate the relationship between fragile histidine triad(FHIT) transcription abnormalities and HPV16 infection and human cervical tumorigenesis.Methods Total RNA from 5 cervical carcinoma cell lines(SiHa,HeLa,RJC-1,CS1213 and C4-1),58 primary cervical cancer specimens and 18 normal cervical epithelial tissues were extracted and FHIT transcripts were characterized by a two-step(nested) reverse transcription(RT)-PCR.The seven of the PCR products with different size were purified and sequenced.HPV16 infection was assessed by PCR.Results ① There were altered FHIT transcripts in SiHa,HeLa and C4-1 cells.Aberrant FHIT transcripts were detected in 39 out of the 58 cervical cancer samples(67.2%),but none out of 18 in the normal cervix tissue specimens(0%);HPV16 infections were identified in 37 of the 58 cervical cancer tissues(63.8%),but 1 in the 18 normal cervical epithelial tissues(5%),which showed a significant difference between these two groups(P0.05).③ The exon 5 and exon 6 were mainly deleted in the altered FHIT transcripts and no insertion and point mutation were found by DNA sequencing.Conclusion Aberrant FHIT expression was significantly common in cervical cancers and was correlated with HPV16 infection.These findings suggest that the tumor suppressor gene FHIT and high risk HPV16 may play a very important role in human cervical carcinogenesis.