Terry Stephane, Queires Luis, Gil-Diez-de-Medina Sixtina, Chen Min-Wei, de la Taille Alexandre, Allory Yves, Tran Phuong-Lan, Abbou Claude C, Buttyan Ralph, Vacherot Francis
Department of Urology and Pathology of CHU Henri Mondor, INSERM E 03-37, Université Paris XII, Centre de Recherches Chirurgicales, Assistance Publique des Hôpitaux de Paris, Créteil, France.
Prostate. 2006 Jul 1;66(10):1100-13. doi: 10.1002/pros.20446.
Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate tissues.
LNCaP cells transfected with PCDH-PC were tested for their ability to grow in vitro and in vivo in androgen-deprived conditions. PCDH-PC mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ hybridization.
PCDH-PC expression induced Wnt signaling in CaP cells and permitted androgen-independent growth of hormone-sensitive CaP cells. Expression of PCDH-PC-homologous transcripts was low and restricted to some epithelial cells in normal tissue and to CaP cells in tumors. However, hormone-resistant CaP cells expressed significantly higher levels of PCDH-PC-related mRNA.
Our findings suggest a novel mechanism for the progression of CaP involving expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes malignant behavior and hormone-resistance of CaP cells.
原钙黏蛋白-PC(PCDH-PC)在LNCaP人前列腺癌细胞系的抗凋亡亚系中表达上调。在此,我们评估PCDH-PC在前列腺癌细胞中的作用及其在人前列腺组织中的mRNA表达。
检测转染PCDH-PC的LNCaP细胞在雄激素剥夺条件下的体外和体内生长能力。通过半定量RT-PCR和原位杂交评估PCDH-PC mRNA表达。
PCDH-PC表达在前列腺癌细胞中诱导Wnt信号,并使激素敏感的前列腺癌细胞实现雄激素非依赖性生长。PCDH-PC同源转录本在正常组织中的表达较低,局限于一些上皮细胞,在肿瘤中则局限于前列腺癌细胞。然而,激素抵抗性前列腺癌细胞表达的PCDH-PC相关mRNA水平显著更高。
我们的研究结果提示了一种涉及PCDH-PC表达的前列腺癌进展新机制。这种新型原钙黏蛋白诱导Wnt信号,促进前列腺癌细胞的恶性行为和激素抵抗。