Horvath Lisa G, Henshall Susan M, Kench James G, Turner Jennifer J, Golovsky David, Brenner Phillip C, O'Neill Gordon F, Kooner Raji, Stricker Phillip D, Grygiel John J, Sutherland Robert L
Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
Prostate. 2004 May 15;59(3):234-42. doi: 10.1002/pros.10361.
The role of the bone morphogenetic protein (BMP) pathway in prostate cancer (PC) is unclear. This study aimed to characterize aspects of the BMP pathway in PC by assessing BMP2, Smad8, and Smad4 expression in normal, hyperplastic, and malignant prostate tissue, and to correlate findings with progression to PC.
Radical prostatectomy (RP) specimens from 74 patients with clinically localized PC (median follow-up 51 months, range 15-152), 44 benign prostatic hypertrophy (BPH) lesions, and 4 normal prostates (NPs) were assessed for BMP2, Smad8, and Smad4 expression using immunohistochemistry.
Both BMP2 (P < 0.001) and nuclear Smad4 (P < 0.0001) expression were significantly decreased in PC compared to benign prostate tissue. Nuclear Smad8 was present in normal/benign prostate tissue but absent in PC and adjacent hyperplasia. Furthermore, loss of BMP2 (P < 0.001) and decreased nuclear Smad4 (P = 0.05) expression correlated with increasing Gleason score.
These data suggest that decreased BMP2, nuclear smad8 and nuclear Smad4 expression are associated with the progression to PC, and in particular loss of BMP2 and Smad4 are related to progression to a more aggressive phenotype.
骨形态发生蛋白（BMP）通路在前列腺癌（PC）中的作用尚不清楚。本研究旨在通过评估正常、增生和恶性前列腺组织中BMP2、Smad8和Smad4的表达来表征PC中BMP通路的各个方面，并将研究结果与PC的进展相关联。
使用免疫组织化学评估了74例临床局限性PC患者（中位随访51个月，范围15 - 152个月）的根治性前列腺切除术（RP）标本、44例良性前列腺增生（BPH）病变和4例正常前列腺（NP）中BMP2、Smad8和Smad4的表达。
与良性前列腺组织相比，PC中BMP2（P < 0.001）和核Smad4（P < 0.0001）的表达均显著降低。核Smad8存在于正常/良性前列腺组织中，但在PC和相邻增生组织中不存在。此外，BMP2的缺失（P < 0.001）和核Smad4表达的降低（P = 0.05）与Gleason评分增加相关。
这些数据表明，BMP2、核smad8和核Smad4表达的降低与PC的进展相关，特别是BMP2和Smad4的缺失与进展为更具侵袭性的表型有关。
