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ID1‐, ID2‐, and ID3‐regulated gene expression in E2A positive or negative prostate cancer cells
Author(s) -
Asirvatham Ananthi J.,
Carey Jason P.W.,
Chaudhary Jaideep
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20633
Subject(s) - prostate cancer , cancer research , prostate , cancer , gene , biology , gene expression , medicine , genetics
Background The inhibitor of differentiation (Id) proteins are expressed in prostate cancer (PCA). However, there is a general lack of Id isoform‐specific downstream effectors. Methods Id1 , Id2 , or Id3 were silenced in PCA cell lines LNCaP, DU145, and PC3 using gene‐specific small interfering RNA (siRNA). The effect of Id gene silencing on representative genes involved in apoptosis (p53, SNAIL2 ), proliferation (p21, p16), and tumor invasion ( E‐cadherin and MMP9 ) was investigated by real‐time PCR. Expression of E‐proteins, the primary Id interaction partners was also evaluated to understand the molecular mechanism of action. Results The Id proteins regulated the expression of CDKNIs p16 and p21 even in the absence of E‐proteins. Loss of Id1 and Id3 up‐ or downregulated E‐cadherin expression in E‐protein negative or positive PCA cell lines, respectively. The effect of Id genes on cell proliferation was also independent of CDKNIs in p16 and p21 null PC3 cells. The p53‐independent anti‐apoptotic effect of Id2 was mediated in part by transcriptional repressor SNAI2 . MMP9 seems to be the common target of all three Id genes ( Id1 , Id2 , and Id3 ). Conclusions The overall effect of Id proteins on proliferation and apoptosis is independent of E‐proteins. E‐proteins can however determine the magnitude of response or in some cases even reverse the Id‐mediated target gene expression. Evaluating E‐protein expression in conjunction with Id proteins will allow better understanding of the molecular mechanism of action of Id proteins and increase their prognostic significance in PCA. Prostate 67: 1411–1420, 2007. © 2007 Wiley‐Liss, Inc.