HOXB13 promotes ovarian cancer progression.
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.
Miao
Jiangyong
J
Molecular Pathology Research Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Wang
Zuncai
Z
Provencher
Heather
H
Muir
Beth
B
Dahiya
Sonika
S
Carney
Erin
E
Leong
Chee-Onn
CO
Sgroi
Dennis C
DC
Orsulic
Sandra
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D018450:Disease Progression; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology
C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D013629:Tamoxifen; D004958:Estradiol