Non-redundant inhibitor of differentiation (Id) gene expression and function in human prostate epithelial cells.
BACKGROUND
The four Id (inhibitor of differentiation) proteins (Id1, Id2, Id3, and Id4) dimerize and neutralize the transcriptional activity of basic helix-loop-helix (bHLH) proteins. The Id proteins negatively regulate differentiation and promote proliferation hence the expression of specific subsets of Id proteins is high in many different types of cancers. However, the expression of all the Id isoforms and their potential function in specific cancer cell types is not known. In this study, the expression and function of all four Id isoforms in prostate cancer cell lines was investigated to gain a better understanding of the role of each Id isoform in normal prostate epithelial and prostate cancer cells.


METHODS
Id gene and protein expression was evaluated in the context of androgen response. The cellular function of Id isoforms was evaluated by targeted loss of function of Id genes.


RESULTS
The four Id isoforms are differentially expressed and regulated in normal human prostate epithelial cells versus prostate cancer cell lines DU145 and LNCaP. Id4 is present only in AR positive cells (normal and LNCaP) and its expression regulated by androgens. Loss of Id1 and Id3 expression by siRNA results in loss of proliferation. Loss of Id2 had no effect on proliferation but increased apoptosis.


CONCLUSIONS
A complex equilibrium between Id isoforms determines the cell fate. Id1 and Id3 target cellular proliferation, Id2 targets apoptosis, and Id4 may act as a potential tumor suppressor in prostate epithelial cells.
Center For Reproductive Biology, Washington State University, Pullman, Washington, USA.
Ananthi J
AJ
Asirvatham
Michelle A
MA
Schmidt
Jaideep
J
Chaudhary
D000728:Androgens / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004848:Epithelium / Q000737:chemistry / Q000502:physiology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D052138:Genes, Neoplasm / Q000502:physiology; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics* / Q000502:physiology*; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D020033:Protein Isoforms; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000728:Androgens; D051796:Inhibitor of Differentiation Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering