Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fragile histidine triad (FHIT) gene, a candidate tumor suppressor gene located at 3p14.2, has been shown to be involved in carcinogenesis of many human tissues, including digestive tract tissues. However, the expression and role of FHIT in the initiation and the development of the colorectal cancer (CRC) are poorly understood. In our present study, we have demonstrated that the FHIT gene exhibits significantly decreased expression in human CRC compared to colorectal adenoma and normal colorectal tissue by tissue microarray (TMA). The positive of FHIT gene expression in normal colorectal tissue, adenoma and adenocarcinoma were 93.75%, 68.75% and 46.25%, respectively. We showed that decreased FHIT expression was significantly correlated with the progression of colorectal carcinoma (P<0.05) as well as differentiation and lymph node metastasis (P<0.05). Two somatic mutations in the FHIT gene were also detected in human CRC. The presence of these mutations correlated significantly with decreased FHIT expression in the human CRC. In addition, we identified decreased FHIT expression resulting in apoptosis inhibition and decreasing apoptosis associated with abnormal levels of some pro- and anti-apoptotic proteins (Bax, Bcl-2 and Survivin) by TUNEL and TMA. Our results demonstrated that the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT, inactivated specifically in human CRC, and contributes to our understanding of the mechanism of colorectal carcinogenesis.
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PMID:Down-regulation of FHIT inhibits apoptosis of colorectal cancer: mechanism and clinical implication. 1738 35

Fragile histidine triad (FHIT) is a tumor suppressor protein that regulates cancer cell proliferation and apoptosis. However, its exact mechanism of action is poorly understood. Phosphatidylinositol 3-OH kinase (PI3K)-Akt-survivin is an important signaling pathway that was regulated by FHIT in lung cancer cells. To determine whether FHIT can regulate this pathway in cholangiocarcinoma QBC939 cells, we constructed an FHIT expression plasmid and used it to transfect QBC939 cells. Protein and mRNA expression were measured by western blotting and qRT-PCR, respectively. The viability and apoptosis of QBC939 cells were then assessed using MTT assays and flow cytometry. Our results revealed that the expression of survivin and Bcl-2 was downregulated, and caspase 3 was upregulated, in cells overexpressing FHIT. In addition, FHIT suppressed the phosphorylation of Akt. The changes in cell proliferation and apoptosis were obvious in cells overexpressing FHIT which parallels that of treatment with LY294002, a potent inhibitor of phosphoinositide 3-kinases. Treatment with LY294002 further decreased the expression of survivin and Bcl-2 and increased caspase-3 levels. These results suggest that FHIT can block the PI3K-Akt-survivin pathway by suppressing the phosphorylation of Akt and the expression of survivin and Bcl-2 and upregulating caspase 3.
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PMID:Fragile histidine triad (FHIT) suppresses proliferation and promotes apoptosis in cholangiocarcinoma cells by blocking PI3K-Akt pathway. 2475 11