Potential role of the human Ha-ras oncogene in the inhibition of gap junctional intercellular communication

✍ Scribed by Mohamed H. El-Fouly; James E. Trosko; Chia-Cheng Chang; Stephen T. Warren

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 598 KB
• Volume: 2
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.2940020305

✦ Synopsis

The modulation of gap junctional intercellular communication (GJIC) plays an important role during tumor promotion. Several tumor-promoting agents are known t o inhibit this form o f cellular coupling. In addition, tumor cells and cells expressing certain oncogenic products have been shown t o exhibit inhibited or reduced GJIC. The Ha-ras oncogene is expressed in a wide variety of human tumors from different tissues. Its p21 product is a membrane-bound polypeptide, the function o f which is not fully characterized. We tested the effects o f the expression of the human c-Ha-ras-I oncogene, derived from the EJ/T4 bladder carcinoma cell line, on the ability of the Chinese hamster V79 cells to conduct gap junctional communication. The junctional competence was studied by t w o different methods, the scrape-loadingidye transfer technique and the metabolic cooperation assay. The results indicate a strong correlation between the expression of p21 ras protein and the inhibition of gap junctional function. Assuming that reversible inhibition of intercellular communication plays a role during tumor promotion and stable inhibition during the tumor progression phase of carcinogenesis, our data suggest that, while chemical tumor promoters and the ras oncogenes might work by different biochemical mechanisms, they both affect a critical cellular function; namely, GJIC.