title: Pigment epithelium-derived factor inhibits caveolin-induced interleukin-8 gene expression and proliferation of human prostate cancer cells.
abstract: Caveolin-1 (Cav), a primary protein component of caveolae, is overexpressed in prostate cancer, thereby promoting growth and metastasis of this tumor. By contrast, pigment epithelium-derived factor (PEDF) has been shown to inhibit tumor growth and metastasis, including that of prostate cancer, via its anti-angiogenic and anti-inflammatory effects. Although it was recently demonstrated that PEDF binds to Cav and blocks its pro-inflammatory actions in endothelial cells, it remains unclear whether PEDF also inhibits the tumor-promoting effects of Cav in cultured prostate cancer cells. The present study examined the effects of PEDF on cell growth, in addition to the gene expression of interleukin-8 (IL-8), which is involved in prostate cancer progression, in the PC-3 human prostate cancer cell line. Exogenous Cav led to a dose-dependent upregulation of the mRNA expression of IL-8 in PC-3 cells, which was blocked by treatment with 1 or 10 nM PEDF, or following the overexpression of small interfering RNAs directed against Cav. Cav (10 nM) increased DNA synthesis in PC-3 cells, which was again suppressed by the administration of 10 nM PEDF. The results of the present study indicated that PEDF may inhibit Cav-induced increases in IL-8 gene expression and proliferation of PC-3 cells. Therefore, the suppressive effects of PEDF in prostate cancer may, in part, be ascribed to its inhibitory actions on Cav.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ojima
authors.affiliation: Department of Chemistry, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higashimoto
authors.affiliation: Department of Chemistry, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Taira
authors.affiliation: Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fukami
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Sho-Ichi
authors.initials: SI
authors.lastname: Yamagishi
keywords: Caveolin-1; angiogenesis; interleukin-8; pigment epithelium-derived factor; prostate cancer cells