title: ID1-, ID2-, and ID3-regulated gene expression in E2A positive or negative prostate cancer cells.
abstract: 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.
authors.affiliation: Department of Biology, Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, Georgia 30314, USA.
authors.forename: Ananthi J
authors.initials: AJ
authors.lastname: Asirvatham
authors.forename: Jason P W
authors.initials: JP
authors.lastname: Carey
authors.forename: Jaideep
authors.initials: J
authors.lastname: Chaudhary
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051796:Inhibitor of Differentiation Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C407909:TCF3 protein, human