Vaz Cátia V, Maia Cláudio J, Marques Ricardo, Gomes Inês M, Correia Sara, Alves Marco G, Cavaco José E, Oliveira Pedro F, Socorro Sílvia
CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
Prostate. 2014 Sep;74(12):1189-98. doi: 10.1002/pros.22835. Epub 2014 Jun 29.
Regucalcin (RGN) is a calcium (Ca(2+) )-binding protein underexpressed in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated.
Androgens are implicated in the promotion of prostate cell proliferation, thus we studied the in vivo effect of androgens on RGN expression in rat prostate. The role of RGN modulating cell proliferation and apoptotic pathways in rat prostate was investigated using transgenic animals (Tg-RGN) overexpressing the protein.
In vivo stimulation with 5α-dihydrotestosterone (DHT) down-regulated RGN expression in rat prostate. Cell proliferation index and prostate weight were reduced in Tg-RGN, which was concomitant with altered expression of cell-cycle regulators. Tg-RGN presented diminished expression of the oncogene H-ras and increased expression of cell-cycle inhibitor p21. Levels of anti-apoptotic Bcl-2, as well as the Bcl-2/Bax protein ratio were increased in prostates overexpressing RGN. Both caspase-3 expression and enzyme activity were decreased in the prostates of Tg-RGN.
Overexpression of RGN resulted in inhibition of cell proliferation and apoptotic pathways, which demonstrated its role maintaining prostate growth balance. Thus, deregulation of RGN expression may be an important event favoring the development of prostate cancer. Moreover, the DHT effect down-regulating RGN expression in rat prostate highlighted for the importance of this protein in prostatic physiology.
调节钙素（RGN）是一种钙（Ca(2+)）结合蛋白，与非肿瘤性前列腺组织或良性前列腺增生病例相比，在前列腺腺癌中表达下调。此外，RGN表达与前列腺腺癌的细胞分化呈负相关，提示RGN的缺失可能与肿瘤的发生和进展有关。然而，RGN对前列腺细胞生长控制的作用尚未得到研究。
雄激素参与促进前列腺细胞增殖，因此我们研究了雄激素对大鼠前列腺中RGN表达的体内作用。使用过表达该蛋白的转基因动物（Tg-RGN）研究RGN在调节大鼠前列腺细胞增殖和凋亡途径中的作用。
用5α-双氢睾酮（DHT）进行体内刺激可下调大鼠前列腺中RGN的表达。Tg-RGN中的细胞增殖指数和前列腺重量降低，这与细胞周期调节因子表达的改变相伴。Tg-RGN中癌基因H-ras的表达降低，细胞周期抑制剂p21的表达增加。在过表达RGN的前列腺中，抗凋亡蛋白Bcl-2的水平以及Bcl-2/Bax蛋白比值均升高。Tg-RGN前列腺中的半胱天冬酶-3表达和酶活性均降低。
RGN的过表达导致细胞增殖和凋亡途径受到抑制，这证明了其在维持前列腺生长平衡中的作用。因此，RGN表达失调可能是促进前列腺癌发生发展的一个重要事件。此外，DHT下调大鼠前列腺中RGN表达的作用突出了该蛋白在前列腺生理学中的重要性。
