Yang G, Truong L D, Timme T L, Ren C, Wheeler T M, Park S H, Nasu Y, Bangma C H, Kattan M W, Scardino P T, Thompson T C
Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
Clin Cancer Res. 1998 Aug;4(8):1873-80.
To identify genes associated with prostate cancer progression, we developed a strategy involving the use of differential display-PCR with a panel of genetically matched primary tumor- and metastasis-derived mouse prostate cancer cell lines. We isolated a cDNA fragment with homology to the mouse caveolin-1 gene. Northern blotting with this fragment revealed increased caveolin expression in metastasis-derived cell lines relative to primary tumor-derived cell lines. Western blotting with a polyclonal caveolin antibody confirmed increased caveolin protein in metastasis-derived mouse cell lines and expression in three of four human prostate cancer cell lines. Immunohistochemical analysis of a human prostate cancer cell line demonstrated a prominent granular pattern of caveolin accumulation. Subsequent analysis of mouse and human prostate specimens revealed minimal caveolin expression in normal epithelium with abundant staining of smooth muscle and endothelium. The frequency of caveolin-positive cells was increased in prostate cancer with markedly increased accumulation of caveolin and a granular staining pattern in lymph node metastatic deposits. In human breast cancer specimens, increased caveolin staining was detected in intraductal and infiltrating ductal carcinoma as well as nodal disease. Caveolin therefore appears to be associated with human prostate cancer progression and is also present in primary and metastatic human breast cancer.
为了鉴定与前列腺癌进展相关的基因，我们开发了一种策略，该策略涉及使用差异显示聚合酶链反应（differential display-PCR），并结合一组基因匹配的原发性肿瘤和转移来源的小鼠前列腺癌细胞系。我们分离出了一个与小鼠小窝蛋白-1（caveolin-1）基因具有同源性的cDNA片段。用该片段进行Northern印迹分析显示，相对于原发性肿瘤来源的细胞系，转移来源的细胞系中小窝蛋白的表达增加。用多克隆小窝蛋白抗体进行Western印迹分析证实，转移来源的小鼠细胞系中小窝蛋白的蛋白水平增加，并且在四个人前列腺癌细胞系中的四个中有三个表达。对一个人前列腺癌细胞系进行免疫组织化学分析显示，小窝蛋白积累呈现出明显的颗粒状模式。随后对小鼠和人前列腺标本的分析显示，正常上皮中小窝蛋白表达极少，而平滑肌和内皮细胞有丰富的染色。在前列腺癌中，小窝蛋白阳性细胞的频率增加，在淋巴结转移灶中小窝蛋白的积累明显增加且呈颗粒状染色模式。在人乳腺癌标本中，在导管内癌、浸润性导管癌以及淋巴结病变中均检测到小窝蛋白染色增加。因此，小窝蛋白似乎与人类前列腺癌进展相关，并且也存在于原发性和转移性人类乳腺癌中。
