BCL-2 ONCOGENE BLOCKS DIFFERENTIATION AND EXTENDS VIABILITY BUT DOES NOT IMMORTALIZE NORMAL HUMAN KERATINOCYTES

Abstract

To ascertain whether the bcl-2 oncogene plays a role in the initial stages of skin carcinogenesis by preventing differentiation of epidermal keratinocytes, we transfected primary human keratinocytes with the human bcl-2 gene and then determined whether these transfectants escape high calcium- and serum-induced differentiation. We found that the bcl-2 oncogene blocked differentiation and extended the life span of human keratinocytes in culture by over 24 weeks compared with cells transfected with pZip-neo DNA, which only grew for 5 weeks in culture. Keratinocytes transfected with the bcl-2 oncogene exhibited apoptotic bodies and telomere-telomere association between chromosomes toward the end of their life-span. These results suggest that die bcl-2 oncogene may be necessary but not sufficient for the immortalization of human keratinocytes.