RhoC expression level is correlated with the clinicopathological characteristics of ovarian cancer and the expression levels of ROCK-I, VEGF, and MMP9

Gynecol Oncol. 2010 Mar;116(3):563-71. doi: 10.1016/j.ygyno.2009.11.015.

Abstract

Objective: To determine the clinicopathological significance of RhoC expression in human ovarian cancer and its effect on the expression of vascular endothelial growth factor (VEGF), Rho-associated coiled-coil-forming kinase (ROCK), and metal matrix proteinases (MMPs).

Methods: Tissue samples from normal ovaries, benign ovarian tumors, and epithelial ovarian cancer were collected. The mRNA and protein expression levels of RhoC, ROCK-I, VEGF, and MMP9 were assessed using reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot, and compared to the clinicopathological characteristics of the sample of origin using the Pearson method of correlation analysis. Small interfering RNA (siRNA) was also used to target RhoC expression in the OVCAR3 and CaOV3 ovarian cancer cell lines, after which cell invasion and migration assays were performed, and the expression of ROCK-I, VEGF, and MMP9 was evaluated.

Results: The expression levels of RhoC, ROCK-I, VEGF, and MMP9 mRNA and protein were significantly higher in ovarian cancer, showing a correlation with clinical stage but not histological type. RhoC expression was positively correlated with ROCK-I, VEGF, and MMP9 expression. Decreased RhoC expression in siRNA-targeted cells inhibited their ability to invade and migrate, as well as inhibiting ROCK-I, VEGF, and MMP9 expression.

Conclusion: The expression level of RhoC is correlated to clinical stage and vascularization in ovarian cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Female
  • Humans
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase Inhibitors
  • Middle Aged
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Transfection
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics
  • Young Adult
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / biosynthesis*
  • rho GTP-Binding Proteins / genetics
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / biosynthesis*
  • rho-Associated Kinases / genetics
  • rhoC GTP-Binding Protein

Substances

  • Matrix Metalloproteinase Inhibitors
  • RNA, Messenger
  • RNA, Small Interfering
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • rho-Associated Kinases
  • Matrix Metalloproteinase 9
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein