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Negative acting HLH proteins Id 1, Id 2, Id 3, and Id 4 are expressed in prostate epithelial cells
Jaideep Chaudhary1, Michelle Schmidt, Ingrid Sadler-Riggleman
1Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4231, USA. jaideep@wsu.edu
Insights
The four Id proteins (Id 1-4) are expressed in normal prostate cells. Id 1 promotes proliferation, while Id 2 and Id 4 regulate differentiation in response to hormones and growth factors.
Area of Science:
- Molecular Biology
- Cell Biology
- Prostate Cancer Research
Background:
- Id proteins (Id 1-4) are dominant negative helix-loop-helix (HLH) proteins that inhibit basic helix loop proteins (bHLH) by preventing DNA binding.
- Id proteins can also modulate non-bHLH proteins like retinoblastoma (Rb) and ETS-TCF.
- Id 1 and Id 2 are implicated in cancer proliferation, but their roles in normal prostate tissue are unclear.
Purpose of the Study:
- To investigate the expression profile of all four Id isoforms (Id 1, Id 2, Id 3, Id 4) in normal rat prostate epithelial cells.
- To determine the functional significance of Id isoforms in prostate epithelial cell regulation.
Main Methods:
- Evaluation of Id isoform expression in normal rat prostate epithelial cells.
- Analysis of Id isoform regulation by growth factors, hormones, and mitogens.
Main Results:
- All four Id isoforms (Id 1, Id 2, Id 3, Id 4) are expressed in normal prostate epithelial cells at varying levels.
- Serum, a growth promoter, increases Id 1, Id 2, and Id 3 levels.
- Testosterone and hepatocyte growth factor (HGF) stimulate Id 4 and Id 2, respectively, promoting differentiation.
Conclusions:
- Id 1 appears to be specifically involved in promoting prostate epithelial cell proliferation.
- Id 4 and Id 2 play distinct roles in regulating differentiated functions in response to androgens and paracrine factors like HGF.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
