Negative acting HLH proteins Id1, Id2, Id3, and Id4 are expressed in prostate epithelial cells

Abstract

The four known Id proteins, Id 1, Id 2, Id 3, and Id 4 are largely considered as dominant negative helix-loop-helix (HLH) proteins. They can dimerize with basic helix loop proteins (bHLH) but the dimers fail to bind the consensus E box response element (CANNTG). Alternatively, members of the Id family, for example, Id 2 can also bind to non-bHLH proteins such as retinoblastoma (Rb) and ETS-TCF to modulate their activities. Consistent with their role as promoters of proliferation, subset of Id genes for example, Id 1 and Id 2 are expressed in many cancers including that of the prostate. However, their expression and function in the normal prostate is unknown. The present study was designed to evaluate the expression profile and functional significance of all Id isoforms in normal rat prostate epithelial cells. The data suggests that all four Id isoforms are expressed in normal cells, albeit at different levels. Agents that promote growth, for example, serum increase the levels of Id 1, Id 2, and Id 3. The hormones and mitogens such as testosterone and hepatocyte growth factor (HGF) that promote prostate epithelial cell differentiation stimulate Id 4 and Id 2, respectively. In prostate epithelial cells, Id 1 may be specifically involved in promoting proliferation whereas Id 4 and Id 2 may have defined roles in regulating differentiated functions in response to androgens and local paracrine factors such as HGF.