Role of hedgehog signaling in ovarian cancer

Resham Bhattacharya, Junhye Kwon, Bushra Ali, Enfeng Wang, Sujata Patra, Vijayalakshmi Shridhar, Priyabrata Mukherjee

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Purpose: In humans, several distinctive cancers result from mutations that aberrantly activate hedgehog (HH) signal transduction. Here, we investigate the role of HH signaling in ovarian cancer. Experimental Design: We assessed the expression of different components of hedghehog pathway in primary tumor samples and cell lines. We used specific hedghehog pathway blocker to study the effect on clonal growth and proliferation of ovarian cancer cell both in vitro and in vivo. Results: We show that the up-regulation of several HH pathway components is a common feature of primary ovarian tumors and cell lines. However, expression of PATCHED1 (PTCH1), a direct transcriptional target of the HH pathway, is down-regulated in ovarian cancer in direct contrast to the expression observed in other adult solid tumors. Cyclopamine, a specific HH pathway inhibitor, inhibits the proliferation and clonal growth of ovarian tumor cells in vitro and arrests ovarian tumor growth in vivo.Expression of BMI-1, a polycomb gene, is down-regulated in ovarian cancer cells following cyclopamine treatment. Overexpression of PTCH1 phenocopied the effects of cyclopamine; it down-regulated BMI-1 and reduced clonal growth in ovarian cancer cell lines. Furthermore, knocking down BMI-1 using small interfering RNA also inhibited the clonal growth of all the ovarian cancer cell lines tested. Conclusions: In brief, the constitutive low-level expression of PTCH1 contributes to proliferation and clonal growth of ovarian cancer cells by an aberrant HH signal. Because the HH pathway can be inhibited by specific inhibitors, these findings point toward possible new treatments to inhibit ovarian cancer growth.

Original languageEnglish (US)
Pages (from-to)7659-7666
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number23
DOIs
StatePublished - Dec 1 2008

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Ovarian Neoplasms
Growth
Tumor Cell Line
Neoplasms
Cell Line
Small Interfering RNA
Signal Transduction
Research Design
Up-Regulation
Mutation
Genes
cyclopamine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bhattacharya, R., Kwon, J., Ali, B., Wang, E., Patra, S., Shridhar, V., & Mukherjee, P. (2008). Role of hedgehog signaling in ovarian cancer. Clinical Cancer Research, 14(23), 7659-7666. https://doi.org/10.1158/1078-0432.CCR-08-1414

Role of hedgehog signaling in ovarian cancer. / Bhattacharya, Resham; Kwon, Junhye; Ali, Bushra; Wang, Enfeng; Patra, Sujata; Shridhar, Vijayalakshmi; Mukherjee, Priyabrata.

In: Clinical Cancer Research, Vol. 14, No. 23, 01.12.2008, p. 7659-7666.

Research output: Contribution to journalArticle

Bhattacharya, R, Kwon, J, Ali, B, Wang, E, Patra, S, Shridhar, V & Mukherjee, P 2008, 'Role of hedgehog signaling in ovarian cancer', Clinical Cancer Research, vol. 14, no. 23, pp. 7659-7666. https://doi.org/10.1158/1078-0432.CCR-08-1414
Bhattacharya R, Kwon J, Ali B, Wang E, Patra S, Shridhar V et al. Role of hedgehog signaling in ovarian cancer. Clinical Cancer Research. 2008 Dec 1;14(23):7659-7666. https://doi.org/10.1158/1078-0432.CCR-08-1414
Bhattacharya, Resham ; Kwon, Junhye ; Ali, Bushra ; Wang, Enfeng ; Patra, Sujata ; Shridhar, Vijayalakshmi ; Mukherjee, Priyabrata. / Role of hedgehog signaling in ovarian cancer. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 23. pp. 7659-7666.
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