Abstract 4998: Down-regulation of Hsulf-1 promotes tumorigenicity of ovarian cancer cells

Abstract

Human Sulfatase1 enzyme (HSulf-1) is down-regulated in a majority of ovarian cancer cell lines and primary tumors, but the functional consequence of this downregulation remains unclear. Here, we showed that down-regulation of HSulf-1 by RNA interference in OV202 ovarian cancer cells resulted in an elevated level of phosphorylated AKT. Conversely, over-expression of HSulf-1 in SKOV3 ovarian cancer cells led to decreased phosphorylation of AKT. When cells were treated with CDDP, OV202 cells with knockdown of HSulf-1 displayed more resistance to drug-induced apoptosis, with IC50 value 3-fold higher than cells with non-targeting shRNA, while SKOV3 cells with overexpression of HSulf-1 were more sensitive to drug-induced apoptosis compared to the control cells. Moreover, knockdown of HSulf-1 also endowed ovarian cancer cells with increased resistance to detachment-induced apoptosis (anoikis). Cell proliferation assays revealed that knockdown of HSulf-1 significantly accelerated cell proliferation of ovarian cancer cells in vitro. Importantly, when cells were injected subcutaneously, 7 of 8 (87.5%) nude mice developed tumors with HSulf-1 knockdown cells within 2 weeks. However, none of the mice injected with nontargeted control transduced cells (control group) developed tumors. Four weeks after injection, 8 of 8 (100%) nude mice developed tumors with HSulf-1 down-regulated cells, while only 2 of 5 (40%) mice had tumors in the control group. The average tumor weight was 4.2±2.7g per mice in HSulf-1 knockdown group, significantly higher than 0.6±0.3g per mice in the control group. Collectively, these results strongly suggest that down-regulation of HSulf-1 promotes tumorigenicity of ovarian cancer possibly due to elevated activation of AKT pathway.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4998.