The progression of expression of INK4a-ARF tumor-suppress in esophagus carcinoma
- VernacularTitle:INK4a/ARF抑癌基因与食管癌的研究进展
- Author:
Shuangping ZHANG
;
Chunli WANG
- Publication Type:Journal Article
- Keywords:
INK4a-ARF;
Tumor-suppressor genes;
Esophagus carcinoma
- From:
Cancer Research and Clinic
2001;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
The INK4a-ARF locus is located on CDKN2A point in human chromosome 9p21 and is known to encode two functionally distinct tumor-suppressor genes p16INK4a (MTS1/CDKN2/INK4a/p16) and p14ARF, have been shown to play significant roles in cell-cycle regulation in cancer. p16 is encoded by the exon 1a-exon 2-exon 3 transcript and functions as a negative regulator of the cell cycle through its inhibition of cyclin-dependent kinases (CDKs) 4 and 6 and subsequent blockage of the cyclindependent phosphorylation of pRB . Thus, loss of p16 function leads to deregulation of pRB's suppressive block of the G1-to-S transition and cell proliferation. In contrast, p14ARF is encoded by the exon 1?-exon 2 transcript and acts upstream of p53. Biochemical evidence has demonstrated that p14ARF physically interacts with human double minute 2 (HDM2) gene product and consequently stabilizes p53, leading to G1 cell-cycle arrest. Overall, somatic mutation of the INK4a/ARF tumor suppressor locus, resulting in functionally deficient p16 and possibly p14ARF proteins, seems to be a prevalent event in the development of oesophagus carcinoma.
