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.
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 humanprostate 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.
Authors: Hao Geng; Brooks L Rademacher; Janet Pittsenbarger; Chung-Ying Huang; Christopher T Harvey; Marie C Lafortune; Anne Myrthue; Mark Garzotto; Peter S Nelson; Tomasz M Beer; David Z Qian Journal: Cancer Res Date: 2010-04-13 Impact factor: 12.701
Authors: Silvia Coma; Dhara N Amin; Akio Shimizu; Anna Lasorella; Antonio Iavarone; Michael Klagsbrun Journal: Cancer Res Date: 2010-04-13 Impact factor: 12.701
Authors: I Echchgadda; S Kota; I DeLa Cruz; A Sabbah; T Chang; R Harnack; V Mgbemena; B Chatterjee; S Bose Journal: Cancer Gene Ther Date: 2009-05-15 Impact factor: 5.987