Coppe Jean-Philippe, Itahana Yoko, Moore Dan H, Bennington James L, Desprez Pierre-Yves
California Pacific Medical Center, Cancer Research Institute, San Francisco, California 94115, USA.
Clin Cancer Res. 2004 Mar 15;10(6):2044-51. doi: 10.1158/1078-0432.ccr-03-0933.
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.
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.
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.
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.
Id蛋白是碱性螺旋-环-螺旋转录因子的显性负调控因子，可控制多种不同组织中的恶性细胞行为。本研究旨在确定Id-1和Id-2蛋白作为前列腺癌进展分子标志物的潜在作用。
利用免疫组织化学技术，我们测定了67例人类前列腺活检样本中Id-1和Id-2的表达。我们还在LNCaP和PC3前列腺癌细胞系中调控Id-1和Id-2的表达，并确定其对体外侵袭、基质金属蛋白酶分泌和增殖的影响。
在人类前列腺癌体内进展过程中，Id-1和Id-2蛋白均上调，且在高侵袭性前列腺癌细胞中过表达。在体外，Id-1的组成性表达以及程度较轻的Id-2表达，将非侵袭性LNCaP前列腺癌细胞转化为增殖性和侵袭性更强的细胞，并增加其基质金属蛋白酶的分泌。相反，高转移性PC3细胞中Id-2表达的下调降低了其生长潜力和侵袭性。
我们认为Id-1和Id-2蛋白均控制前列腺癌细胞表型，并可作为侵袭性人类前列腺癌的分子标志物。
