Id-1 and Id-2 Proteins as Molecular Markers for Human Prostate Cancer Progression

• Published in: Clinical cancer research 2004-03, Vol.10 (6), p.2044-2051
• Main Authors: COPPE, Jean-Philippe, ITAHANA, Yoko, MOORE, Dan H, BENNINGTON, James L, DESPREZ, Pierre-Yves
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cell Line, Tumor; Disease Progression; DNA-Binding Proteins - analysis; DNA-Binding Proteins - genetics; Helix-Loop-Helix Motifs; Humans; Inhibitor of Differentiation Protein 1; Inhibitor of Differentiation Protein 2; Male; Medical sciences; Neoplasm Invasiveness; Pharmacology. Drug treatments; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Repressor Proteins - analysis; Repressor Proteins - genetics; Transcription Factors - analysis; Transcription Factors - genetics; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0933

Purpose: Id proteins are dominant-negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior in many different tissues. This study aimed to identify the potential role of Id-1 and Id-2 proteins as molecular makers for prostate cancer progression. Experimental Design: Using the technique of immunohistochemistry, we determined Id-1 and Id-2 expression in a panel of 67 human prostate biopsies. We also manipulated Id-1 and Id-2 expression in LNCaP and PC3 prostate cancer cell lines and determined the effects on invasion in vitro , matrix metalloproteinase secretion, and proliferation. Results: Both Id-1 and Id-2 proteins were up-regulated during human prostate cancer progression in vivo and were overexpressed in highly aggressive prostate cancer cells. In vitro , constitutive expression of Id-1, and to a lesser extent Id-2, converted nonaggressive LNCaP prostate cancer cells into more proliferative and invasive cells and increased their secretion of matrix metalloproteinases. Conversely, the down-regulation of Id-2 expression in highly metastatic PC3 cells reduced their growth potential and invasiveness. Conclusions: We propose that both Id-1 and Id-2 proteins control prostate cancer cell phenotypes and could serve as molecular markers of aggressive human prostate cancer.