前列腺衍生因子作为雄激素受体阳性人前列腺癌细胞增殖的旁分泌和自分泌因子。

Prostate-derived factor as a paracrine and autocrine factor for the proliferation of androgen receptor-positive human prostate cancer cells.

作者信息

Chen Siu-Ju, Karan Dev, Johansson Sonny L, Lin Fen-Fen, Zeckser Jeffrey, Singh Ajay P, Batra Surinder K, Lin Ming-Fong

机构信息

Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.

出版信息

Prostate. 2007 Apr 1;67(5):557-71. doi: 10.1002/pros.20551.

DOI:10.1002/pros.20551

PMID:17221842

Abstract

BACKGROUND

The expression of prostate-derived factor (PDF) is significantly elevated in human prostate tumors. We investigate the functional role and signaling of PDF in androgen receptor (AR)-positive human prostate cancer cells.

METHODS

Transient or stable expression of PDF by cDNA transfection, antisense-mediated gene silencing, media conditioned by PDF-elevated cells, and antibody (Ab) neutralization were employed.

RESULTS

Elevated endogenous and exogenous expression of PDF and treatment of PDF-enriched media were associated with increased proliferation and clonogenic growth of the cells. On the contrary, knockdown of PDF or addition of PDF neutralizing Ab resulted in diminished proliferation and reduced anchorage-independent growth. Further, ERK1/2 and p90RSK, but not Smad2/3, were activated in PDF-elevated cells as well as in cells treated with PDF-enriched media, while inhibition of ERK1/2 decreased the growth of those cells.

CONCLUSION

PDF promotes AR-positive prostate tumor progression through upregulating cell proliferation via ERK1/2 signal pathway.

摘要

背景

前列腺衍生因子（PDF）在人类前列腺肿瘤中的表达显著升高。我们研究了PDF在雄激素受体（AR）阳性的人类前列腺癌细胞中的功能作用及信号传导。

方法

采用cDNA转染瞬时或稳定表达PDF、反义介导的基因沉默、PDF升高细胞条件培养基以及抗体（Ab）中和等方法。

结果

PDF内源性和外源性表达升高以及用富含PDF的培养基处理与细胞增殖增加和克隆形成生长有关。相反，敲低PDF或添加PDF中和抗体导致增殖减少和非锚定依赖性生长降低。此外，在PDF升高的细胞以及用富含PDF的培养基处理的细胞中，ERK1/2和p90RSK被激活，但Smad2/3未被激活，而抑制ERK1/2可降低这些细胞的生长。