Loss of HSulf-1 expression enhances tumorigenicity by inhibiting Bim expression in ovarian cancer

Xiaoping He, Ashwani Khurana, Debarshi Roy, Scott Kaufmann, Viji Shridhar

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The expression of human Sulfatase1 (HSulf-1) is downregulated in the majority of primary ovarian cancer tumors, but the functional consequence of this downregulation remains unclear. Using two different shRNAs (Sh1 and Sh2), HSulf-1 expression was stably downregulated in ovarian cancer OV202 cells. We found that HSulf-1-deficient OV202 Sh1 and Sh2 cells formed colonies in soft agar. In contrast, nontargeting control (NTC) shRNA-transduced OV202 cells did not form any colonies. Moreover, subcutaneous injection of OV202 HSulf-1-deficient cells resulted in tumor formation in nude mice, whereas OV202 NTC cells did not. Also, ectopic expression of HSulf-1 in ovarian cancer SKOV3 cells significantly suppressed tumor growth in nude mice. Here, we show that HSulf-1-deficient OV202 cells have markedly decreased expression of proapoptotic Bim protein, which can be rescued by restoring HSulf-1 expression in OV202 Sh1 cells. Enhanced expression of HSulf-1 in HSulf-1-deficient SKOV3 cells resulted in increased Bim expression. Decreased Bim levels after loss of HSulf-1 were due to increased p-ERK, because inhibition of ERK activity with PD98059 resulted in increased Bim expression. However, treatment with a PI3 kinase/AKT inhibitor, LY294002, failed to show any change in Bim protein level. Importantly, rescuing Bim expression in HSulf-1 knockdown cells significantly retarded tumor growth in nude mice. Collectively, these results suggest that loss of HSulf-1 expression promotes tumorigenicity in ovarian cancer through regulating Bim expression.

Original languageEnglish (US)
Pages (from-to)1783-1789
Number of pages7
JournalInternational Journal of Cancer
Volume135
Issue number8
DOIs
StatePublished - Oct 15 2014

Keywords

  • Bim
  • HSulf-1
  • ovarian cancer
  • tumorigenicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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