Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer

Xinyu Wu, Yang Zhan, Xin Li, Jianjun Wei, Larion Santiago, Garrett Daniels, Fangming Deng, Xuelin Zhong, Luis Chiriboga, Ross Basch, Sheng Xiong, Yan Dong, Xinmin Zhang, Peng Lee

Research output: Contribution to journalArticle

Abstract

Estrogen receptors (ER) play important roles in the development and progression of breast and ovarian cancers. ERs mediate transcriptional regulation through interaction with cofactors and binding to response elements within the regulatory elements of target genes. Here, we examined the expression and function of TBLR1/TBL1XR1, a core component of NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid receptor) corepressor complexes, in breast and ovarian cancers. We found that although TBLR1 is present in both the nucleus and cytoplasm of normal and neoplastic breast and ovarian cells, it is expressed at significantly higher levels in the nucleus of malignant breast and ovarian cells compared to benign cells. TBLR1 functions as an ER corepressor to inhibit ER-mediated transcriptional activation in both breast and ovarian cell lines, but it has no effect on androgen receptor (AR) mediated transcriptional activation in these cells. Furthermore, ectopic expression of nuclear TBLR1 in breast and ovarian cancer cells stimulates cell proliferation. The increased cell proliferation by nuclear TBLR1 is through both ER-independent and ER-dependent mechanisms as evidenced by increased growth in hormone-free medium and estrogen medium, as well as reduced growth with ER knockdown by siRNA. Nuclear TBLR1 overexpression also increased migration and invasion in both breast and ovarian cancer cells. Determining the functional relationship between TBLR1 and ER may provide insights to develop novel treatment strategies and improve response to hormonal therapy in breast and ovarian cancers.

Original languageEnglish (US)
Pages (from-to)2351-2360
Number of pages10
JournalAmerican Journal of Cancer Research
Volume6
Issue number10
StatePublished - 2016

Fingerprint

Co-Repressor Proteins
Estrogen Receptors
Ovarian Neoplasms
Cell Movement
Cell Proliferation
Breast Neoplasms
Breast
Transcriptional Activation
Retinoic Acid Receptors
Androgen Receptors
Response Elements
Small Interfering RNA
Growth Hormone
Thyroid Gland
Estrogens
Cytoplasm
Cell Line
Growth
Genes

Keywords

  • Breast cancer
  • Estrogen receptor
  • Nuclear TBLR1
  • Ovarian cancer
  • TBL1XR1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer. / Wu, Xinyu; Zhan, Yang; Li, Xin; Wei, Jianjun; Santiago, Larion; Daniels, Garrett; Deng, Fangming; Zhong, Xuelin; Chiriboga, Luis; Basch, Ross; Xiong, Sheng; Dong, Yan; Zhang, Xinmin; Lee, Peng.

In: American Journal of Cancer Research, Vol. 6, No. 10, 2016, p. 2351-2360.

Research output: Contribution to journalArticle

Wu, X, Zhan, Y, Li, X, Wei, J, Santiago, L, Daniels, G, Deng, F, Zhong, X, Chiriboga, L, Basch, R, Xiong, S, Dong, Y, Zhang, X & Lee, P 2016, 'Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer', American Journal of Cancer Research, vol. 6, no. 10, pp. 2351-2360.
Wu, Xinyu ; Zhan, Yang ; Li, Xin ; Wei, Jianjun ; Santiago, Larion ; Daniels, Garrett ; Deng, Fangming ; Zhong, Xuelin ; Chiriboga, Luis ; Basch, Ross ; Xiong, Sheng ; Dong, Yan ; Zhang, Xinmin ; Lee, Peng. / Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer. In: American Journal of Cancer Research. 2016 ; Vol. 6, No. 10. pp. 2351-2360.
@article{a9f2cdf72ffb4a819217fadc9edd91ed,
title = "Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer",
abstract = "Estrogen receptors (ER) play important roles in the development and progression of breast and ovarian cancers. ERs mediate transcriptional regulation through interaction with cofactors and binding to response elements within the regulatory elements of target genes. Here, we examined the expression and function of TBLR1/TBL1XR1, a core component of NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid receptor) corepressor complexes, in breast and ovarian cancers. We found that although TBLR1 is present in both the nucleus and cytoplasm of normal and neoplastic breast and ovarian cells, it is expressed at significantly higher levels in the nucleus of malignant breast and ovarian cells compared to benign cells. TBLR1 functions as an ER corepressor to inhibit ER-mediated transcriptional activation in both breast and ovarian cell lines, but it has no effect on androgen receptor (AR) mediated transcriptional activation in these cells. Furthermore, ectopic expression of nuclear TBLR1 in breast and ovarian cancer cells stimulates cell proliferation. The increased cell proliferation by nuclear TBLR1 is through both ER-independent and ER-dependent mechanisms as evidenced by increased growth in hormone-free medium and estrogen medium, as well as reduced growth with ER knockdown by siRNA. Nuclear TBLR1 overexpression also increased migration and invasion in both breast and ovarian cancer cells. Determining the functional relationship between TBLR1 and ER may provide insights to develop novel treatment strategies and improve response to hormonal therapy in breast and ovarian cancers.",
keywords = "Breast cancer, Estrogen receptor, Nuclear TBLR1, Ovarian cancer, TBL1XR1",
author = "Xinyu Wu and Yang Zhan and Xin Li and Jianjun Wei and Larion Santiago and Garrett Daniels and Fangming Deng and Xuelin Zhong and Luis Chiriboga and Ross Basch and Sheng Xiong and Yan Dong and Xinmin Zhang and Peng Lee",
year = "2016",
language = "English (US)",
volume = "6",
pages = "2351--2360",
journal = "American Journal of Cancer Research",
issn = "2156-6976",
publisher = "e-Century Publishing Corporation",
number = "10",

}

TY - JOUR

T1 - Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer

AU - Wu, Xinyu

AU - Zhan, Yang

AU - Li, Xin

AU - Wei, Jianjun

AU - Santiago, Larion

AU - Daniels, Garrett

AU - Deng, Fangming

AU - Zhong, Xuelin

AU - Chiriboga, Luis

AU - Basch, Ross

AU - Xiong, Sheng

AU - Dong, Yan

AU - Zhang, Xinmin

AU - Lee, Peng

PY - 2016

Y1 - 2016

N2 - Estrogen receptors (ER) play important roles in the development and progression of breast and ovarian cancers. ERs mediate transcriptional regulation through interaction with cofactors and binding to response elements within the regulatory elements of target genes. Here, we examined the expression and function of TBLR1/TBL1XR1, a core component of NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid receptor) corepressor complexes, in breast and ovarian cancers. We found that although TBLR1 is present in both the nucleus and cytoplasm of normal and neoplastic breast and ovarian cells, it is expressed at significantly higher levels in the nucleus of malignant breast and ovarian cells compared to benign cells. TBLR1 functions as an ER corepressor to inhibit ER-mediated transcriptional activation in both breast and ovarian cell lines, but it has no effect on androgen receptor (AR) mediated transcriptional activation in these cells. Furthermore, ectopic expression of nuclear TBLR1 in breast and ovarian cancer cells stimulates cell proliferation. The increased cell proliferation by nuclear TBLR1 is through both ER-independent and ER-dependent mechanisms as evidenced by increased growth in hormone-free medium and estrogen medium, as well as reduced growth with ER knockdown by siRNA. Nuclear TBLR1 overexpression also increased migration and invasion in both breast and ovarian cancer cells. Determining the functional relationship between TBLR1 and ER may provide insights to develop novel treatment strategies and improve response to hormonal therapy in breast and ovarian cancers.

AB - Estrogen receptors (ER) play important roles in the development and progression of breast and ovarian cancers. ERs mediate transcriptional regulation through interaction with cofactors and binding to response elements within the regulatory elements of target genes. Here, we examined the expression and function of TBLR1/TBL1XR1, a core component of NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid receptor) corepressor complexes, in breast and ovarian cancers. We found that although TBLR1 is present in both the nucleus and cytoplasm of normal and neoplastic breast and ovarian cells, it is expressed at significantly higher levels in the nucleus of malignant breast and ovarian cells compared to benign cells. TBLR1 functions as an ER corepressor to inhibit ER-mediated transcriptional activation in both breast and ovarian cell lines, but it has no effect on androgen receptor (AR) mediated transcriptional activation in these cells. Furthermore, ectopic expression of nuclear TBLR1 in breast and ovarian cancer cells stimulates cell proliferation. The increased cell proliferation by nuclear TBLR1 is through both ER-independent and ER-dependent mechanisms as evidenced by increased growth in hormone-free medium and estrogen medium, as well as reduced growth with ER knockdown by siRNA. Nuclear TBLR1 overexpression also increased migration and invasion in both breast and ovarian cancer cells. Determining the functional relationship between TBLR1 and ER may provide insights to develop novel treatment strategies and improve response to hormonal therapy in breast and ovarian cancers.

KW - Breast cancer

KW - Estrogen receptor

KW - Nuclear TBLR1

KW - Ovarian cancer

KW - TBL1XR1

UR - http://www.scopus.com/inward/record.url?scp=84995698734&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995698734&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:84995698734

VL - 6

SP - 2351

EP - 2360

JO - American Journal of Cancer Research

JF - American Journal of Cancer Research

SN - 2156-6976

IS - 10

ER -