Y-27632 Inhibits Myc-Induced Apoptosis And Cooperates With Myc To Immortalize Human Keratinocytes

The high-risk HPV E6 and E7 genes are sufficient to immortalize human foreskin keratinocytes (HFKs) through activation of telomerase and inactivation of the RB/p16 pathway, respectively. Our previous work has shown that Myc (via induction of hTERT) may substitute for E6 and immortalize HFKs when combined with HPV E7. When expressed alone, however, Myc induced p53 expression and apoptosis. In the current study we found that Myc, in combination with the ROCK inhibitor (Y-27632), led immortalization of human foreskin keratinocytes. Our data confirmed that Myc induced apoptosis and blebbing of human keratinocytes when cultured in serum free synthetic medium (KGM) and that Y-27632 rapidly inhibits this process. Thus, our data demonstrate that Myc is capable of independently immortalizing HFKs when apoptosis pathways are blocked. Citation Format: Aleksandra Dakic, Kyle Divito, Shuang Fang, Nancy Palechor-Ceron, Vera Simic, Sujata Choudhury, Songtao Yu, Cynthia M. Simbulan-Rosenthal, Dean Rosenthal, Richard Schlegel, Xuefeng Liu. Y-27632 inhibits Myc-induced apoptosis and cooperates with Myc to immortalize human keratinocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5145. doi:10.1158/1538-7445.AM2015-5145