Faculté de Médecine et des Sciences de la Santé, Service of Endocrinology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Prostate. 2010 Jun 15;70(9):921-33. doi: 10.1002/pros.21126.
Seladin-1 belongs to a subgroup of androgen-dependent genes associated with anti-proliferative, pro-differentiation, and pro-apoptotic functions and plays a protective role against oncogenic stress. The present study aims to investigate the localization and expression of Seladin-1 protein in normal and tumoral human prostatic tissues as well as to explore its role in proliferation and steroid secretion in androgen-dependent (LnCaP) and androgen-independent (DU145) cell lines and in human prostate primary cell culture.
Seladin-1 protein localization and expression were assessed on whole tissue sections by tissue array/immunohistochemistry and following immunofluorescence and Western blotting. Proliferation (Ki67 fluorescence labeling and cell counts) and steroid secretion (ELISA) were assessed in cell lines and primary epithelial cell cultures.
In human prostatic tissue and cells, Seladin-1 was mostly localized within epithelial and rarely within stromal cells and primarily present in secretory luminal cells of normal and tumoral prostate cells. Its expression was increased in low-risk prostate cancer but reduced in advanced prostate cancers when compared to normal tissues. Seladin-1 was highly expressed in LnCaP, whereas its expression level was lower in DU145 cells. Seladin-1 inhibition by treatment with its specific inhibitor, U18666A (75 nM), increased proliferation in LnCaP and primary cell culture, as well as testosterone and dihydrotestosterone levels in both LnCaP and DU145 cell lines.
Seladin-1 involvement in proliferation and secretion suggests that its downregulation may be a major mechanism causing prostate cancer evolution. Seladin-1 may thus potentially decrease cell growth and steroid dependency in low-grade prostate cancer.
Seladin-1 属于雄激素依赖性基因的一个亚群，与抗增殖、促分化和促凋亡功能有关，对致癌应激具有保护作用。本研究旨在研究 Seladin-1 蛋白在正常和肿瘤性人前列腺组织中的定位和表达，并探讨其在雄激素依赖性（LnCaP）和雄激素非依赖性（DU145）细胞系以及人前列腺原代细胞培养中的增殖和类固醇分泌中的作用。
通过组织微阵列/免疫组织化学以及免疫荧光和 Western blot 检测，评估 Seladin-1 蛋白在整个组织切片中的定位和表达。在细胞系和原代上皮细胞培养物中评估增殖（Ki67 荧光标记和细胞计数）和类固醇分泌（ELISA）。
在人前列腺组织和细胞中，Seladin-1 主要位于上皮细胞内，很少位于基质细胞内，主要存在于正常和肿瘤性前列腺细胞的分泌腔细胞内。与正常组织相比，其在低风险前列腺癌中表达增加，但在晚期前列腺癌中表达减少。Seladin-1 在 LnCaP 中高表达，而在 DU145 细胞中表达水平较低。用其特异性抑制剂 U18666A（75 nM）处理 Seladin-1 抑制，可增加 LnCaP 和原代细胞培养物的增殖，以及 LnCaP 和 DU145 细胞系中的睾酮和二氢睾酮水平。
Seladin-1 参与增殖和分泌表明其下调可能是导致前列腺癌进展的主要机制。Seladin-1 可能因此潜在地降低低级别前列腺癌中的细胞生长和类固醇依赖性。
