ICER reverses tumorigenesis of rat prostate tumor cells without affecting cell growth.

Abstract

Inducible cAMP early repressor (ICER) is an important mediator of cAMP antiproliferative activity that acts as a putative tumor suppressor gene product. ICER is a transcriptional repressor that negatively regulates cAMP-mediated gene expression. Here, we report the effect of ectopically increasing the expression of ICER on in vitro and in vivo proliferation of the highly metastatic and androgen-insensitive AT6.3 rat prostate cells. The proliferative potential of stable AT6.3 cell clones expressing ICER was studied by cell counts, thymidine incorporation, flow cytometry, colony formation in soft agar, and growth in immunodeficient nude mice. cAMP inhibits the growth of AT6.3 cells. ICER mRNA and protein levels were markedly induced by cAMP in AT6.3 cells. Forced expression of ICER in AT6.3 cells did not affect cell growth, thymidine incorporation, or the cell cycle. However, these ICER-bearing AT6.3 cells were rendered unable to grow in soft agar or to form tumors in nude mice. These results show that ICER specifically affects the tumorigenicity of prostate cancer cell without affecting their growth. Therefore, the manipulation of ICER expression could be used for the treatment of androgen-insensitive prostate tumors without causing undesirable toxicity to the cells.