HOXB13 promotes ovarian cancer progression

Jiangyong Miao, Zuncai Wang, Heather Provencher, Beth Muir, Sonika Dahiya, Erin Carney, Chee Onn Leong, Dennis C. Sgroi, Sandra Orsulic

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Deregulated expression of HOXB13 in a subset of estrogen receptor-positive breast cancer patients treated with tamoxifen monotherapy is associated with an aggressive clinical course and poor outcome. Because the ovary is another hormone-responsive organ, we investigated whether HOXB13 plays a role in ovarian cancer progression. We show that HOXB13 is expressed in multiple human ovarian cancer cell lines and tumors and that knockdown of endogenous HOXB13 by RNA interference in human ovarian cancer cell lines is associated with reduced cell proliferation. Ectopic expression of HOXB13 is capable of transforming p53 -/- mouse embryonic fibroblasts and promotes cell proliferation and anchorage-independent growth in mouse ovarian cancer cell lines that contain genetic alterations in p53, myc, and ras. In this genetically defined cell line model of ovarian cancer, we demonstrate that HOXB13 collaborates with activated ras to markedly promote tumor growth in vivo and that HOXB13 confers resistance to tamoxifen-mediated apoptosis. Taken together, our results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer.

Original languageEnglish
Pages (from-to)17093-17098
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number43
DOIs
StatePublished - Oct 23 2007

Keywords

  • Estrogen
  • Homeobox
  • Mouse model
  • Ras
  • Tamoxifen

Fingerprint

Dive into the research topics of 'HOXB13 promotes ovarian cancer progression'. Together they form a unique fingerprint.

Cite this