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Decreased fragile histidine triad expression in colorectal cancer and its association with apoptosis inhibition

摘要AIM:To detect the expression of fragile histidine triad(FHIT)in normal colorectal tissue,colorectal adenoma and colorectal cancer(CRC)tissue,and to analyze its relationship with the clinicopathological features of CRC,and apoptosis-associated proteins(Bcl-2,Bax,survivin)and apoptosis in colorectal cancer.METHODS:FHIT mRNA analysis was performed by nested reverse transcription-polymerase chain reaction(RT-PCR)assay.Tissue microarray(TMA)was established to detect the expression of FHIT,Bcl-2,Bax and survivin genes in 80 CRC tissue specimens,16 colorectal adenoma tissue specimens and 16 hemorrhoid (PPH)tissue specimens during the same period of time as the control.Citrate-microwave-SP was used as immunohistochemical method.The relationship between clinicopathological factors,such as differentiation grades and 5-year survival rate was observed.TUNEL assay was used to detect the apoptosis index in 80 CRC tissue specimens.RESULTS:Ten out of 26(38.5%)CRC tissue specimens expressed aberrant FHIT transcripts,none of the aberrant FHIT transcripts was observed in the matched normal tissue and colorectal adenoma tissue by nested RT-PCR assay.The positive rate of FHIT gene expression in normal colorectal tissue,colorectal adenoma and carcinoma tissue was 93.75%,68.75% and 46.25%,respectively.Clinicopathological analysis of patients showed that the decreased FHIT gene expression was not associated with age,sex,serum CEA levels,tumor site and size,histological classification.However,the expression of FHIT was correlated with differentiation grades,pathological stages,lymph node metastases and 5-year survival rate after operation.The positive rate of apoptosis-associated proteins(Bax,Bcl-2 and survivin)in CRC tissue was 72.50%,51.25% and 77.50%,respectively.The expression of these apoptosisassociated proteins in CRC tissue was correlated with the expression of FHIT The mean apoptosis index in FHIT negative tumors was significantly lower than that in FHIT positive tumors(5.41 ± 0.23 vs 0.56 ± 0.10,P < 0.01).CONCLUSION:The FHIT gene plays an important role in the regulation of apoptosis and decreased FHIT expression plays a key role in the initiation and progression of colorectal carcinoma.

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作者单位 Department of Gastrointestinal Surgery,Affiliated Guangzhou First People's Hospital,Guangzhou Medical College,Guangzhou 510180,Guangdong Province,China [1] Center of Hepatic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei Province,China [2] Department of Pathology,Affiliated Guangzhou First People's Hospital,Guangzhou Medical College,Guangzhou 510180,Guangdong Province,China [3] Department of Gastroenterology,Affiliated Guangzhou First People's Hospital,Guangzhou Medical College,Guangzhou 510180,Guangdong Province,China [4]
分类号 R73(肿瘤学)
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发布时间 2007-05-14(万方平台首次上网日期,不代表论文的发表时间)
基金项目
广东省自然科学基金((06020005))
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