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. 2007 Wiley-Liss, Inc
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. 2007 Wiley-Liss, Inc
Authors: M J Gray; N A Dallas; G Van Buren; L Xia; A D Yang; R J Somcio; P Gaur; L S Mangala; P E Vivas-Mejia; F Fan; A M Sanguino; G E Gallick; G Lopez-Berestein; A K Sood; L M Ellis Journal: Oncogene Date: 2008-09-22 Impact factor: 9.867
Authors: Kyle A DiVito; Cynthia M Simbulan-Rosenthal; You-Shin Chen; Valerie A Trabosh; Dean S Rosenthal Journal: Carcinogenesis Date: 2013-12-16 Impact factor: 4.944
Authors: Eva Cubillo; Antonio Diaz-Lopez; Eva P Cuevas; Gema Moreno-Bueno; Hector Peinado; Amalia Montes; Vanesa Santos; Francisco Portillo; Amparo Cano Journal: PLoS One Date: 2013-03-26 Impact factor: 3.240