Reduced messenger RNA expression level of p21CIP1 in human colorectal carcinoma tissues and its association with p53 gene mutation

✍ Scribed by Kazuyuki Matsushita; Susumu Kobayashi; Masataka Kato; Yasushi Itoh; Kazuaki Okuyama; Shigeru Sakiyama; Kaichi Isono

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 631 KB
• Volume: 69
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960822)69:4<259::aid-ijc3>3.0.co;2-w

✦ Synopsis

p2lCipl was first isolated as one of the cyclin-dependent kinase (Cdk) interacting proteins induced by wild-type p53 gene product, and it appears to play an essential regulatory role in the control of cell proliferation as a potent, tight-binding inhibitor of cyclin-Cdk complex that blocks the G,/S transition of the cell cycle. We have now examined the p2lCipl mRNA expression levels in I 6 surgically excised human colorectal tumor and non-tumor tissues by Northern-blot analysis with reference to the identification of p53 gene mutations. p53 gene mutations were detected in 6 tumor tissues but not in the other I 0 tissues by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method and following direct sequencing. The mean p2 I Cip I mRNA expression level in tumor tissues was significantly suppressed compared to that of non-tumor tissues, irrespective of p53 gene mutations. In p53 gene mutation-detected cases, the mean expression level of p2 I Cipl mRNAs of tumor tissues was about 60% of that of cases without p53 gene mutation. Moreover, the relative mRNA expression levels of p2 I Cipl significantly decreased as the pathohistological stages progressed by Dukes' staging system, while in patients with liver metastasis these levels were significantly suppressed compared to those of patients without organ metastasis. These results indicate that reduced expression of p2lCipl mRNA is critical for growth activity and malignant potential of human colorectal carcinoma, and that the decrease in pZ/CipI mRNA level is due to p53 gene mutation as well as other mechanisms during human colorectal carcinogenesis.