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

doi:10.1073/pnas.0707938104

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 journal › Article › peer-review

96 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 language	English
Pages (from-to)	17093-17098
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	104
Issue number	43
DOIs	https://doi.org/10.1073/pnas.0707938104
State	Published - Oct 23 2007

Keywords

Estrogen
Homeobox
Mouse model
Ras
Tamoxifen

Access to Document

10.1073/pnas.0707938104

Cite this

@article{b7e006df2eaa40f1a481608621b8c9c7,

title = "HOXB13 promotes ovarian cancer progression",

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.",

keywords = "Estrogen, Homeobox, Mouse model, Ras, Tamoxifen",

author = "Jiangyong Miao and Zuncai Wang and Heather Provencher and Beth Muir and Sonika Dahiya and Erin Carney and Leong, {Chee Onn} and Sgroi, {Dennis C.} and Sandra Orsulic",

year = "2007",

month = oct,

day = "23",

doi = "10.1073/pnas.0707938104",

language = "English",

volume = "104",

pages = "17093--17098",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

number = "43",

}

TY - JOUR

T1 - HOXB13 promotes ovarian cancer progression

AU - Miao, Jiangyong

AU - Wang, Zuncai

AU - Provencher, Heather

AU - Muir, Beth

AU - Dahiya, Sonika

AU - Carney, Erin

AU - Leong, Chee Onn

AU - Sgroi, Dennis C.

AU - Orsulic, Sandra

PY - 2007/10/23

Y1 - 2007/10/23

N2 - 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.

AB - 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.

KW - Estrogen

KW - Homeobox

KW - Mouse model

KW - Ras

KW - Tamoxifen

UR - http://www.scopus.com/inward/record.url?scp=36749045193&partnerID=8YFLogxK

U2 - 10.1073/pnas.0707938104

DO - 10.1073/pnas.0707938104

M3 - Article

C2 - 17942676

AN - SCOPUS:36749045193

SN - 0027-8424

VL - 104

SP - 17093

EP - 17098

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 43

ER -

HOXB13 promotes ovarian cancer progression

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this