Androgen-repressed phenotype in human prostate cancer
Androgen-repressed phenotype in human prostate cancer
复制标题
DOI：
10.1073/pnas.93.26.15152
复制
发表时间：
1996-12-24
影响因子：
11.1
通讯作者：
Chung, LWK
中科院分区：
文献类型：
--
作者：
Zhau, HYE;Chang, SM;Chung, LWK
建立了雄激素抑制的人前列腺癌Tell系，并对其进行了鉴定。该细胞系来源于一名晚期转移性疾病患者的腹水，与雄激素依赖型LNCaP及其雄激素非依赖性C4-2亚系的行为不同，雄激素和雌激素在体内和体外均以剂量依赖的方式抑制ARCaP细胞的生长，ARCaP具有致瘤性和高转移性。它会将红外线转移到淋巴结。ARCaP细胞表达低水平的雄激素受体mRNA和前列腺特异性抗原的mRNA和蛋白。免疫组织化学染色显示ARCaP细胞对表皮生长因子受体、c-erb B2/neu和c-erb、B3有较强的染色。嗜铬粒蛋白A染色阴性，毛发蛙皮素、5-羟色胺、神经元特异性烯醇化酶和C-MET原癌基因(一种肝生长因子/散布因子受体)阳性。ARCaP细胞还分泌高水平的明胶酶A和B以及一些基质分解素，这表明该细胞系可能含有代表具有选择性神经内分泌表型的侵袭性腺癌的标志物。在抑制生长的同时，通过前列腺特异性抗原启动子-β-半乳糖苷酶报告基因检测，雄激素也被发现抑制前列腺特异性抗原在ARCaP细胞中的表达。我们的结果表明，雄激素抑制状态可能是前列腺癌进展的中心，晚期前列腺癌可以从雄激素非依赖性状态进展到雄激素抑制状态。
An androgen-repressed human prostate cancer tell line, ARCaP, was established and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease, In contrast to the behavior of androgen-dependent LNCaP and its androgen-independent C4-2 subline, androgen and estrogen suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in vitro, ARCaP is tumorigenic and highly metastatic. It metastasizes Ir to the lymph node. lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic hosts, ARCaP cells express low levels of androgen receptor mRNA and prostate-specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c-erb, B3. Staining is negative for chromogranin A and positive fur bombesin, serotonin, neuron-specific enolase, and the C-met protooncogene (a hepatic growth factor/scatter factor receptor). ARCaP cells also secrete high levels of gelatinase A and B and some stromelysin, which suggests that this cell line may contain markers representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also found to repress the expression of prostate-specific antigen in ARCaP cells as detected by a prostate-specific antigen promoter-beta-galactosidase reporter assay. Our results suggest that the androgen-repressed state may be central to prostate cancer progression and that advanced prostate cancer can progress from an androgen-independent to an androgen-repressed state.