SIRT1 is essential for oncogenic signaling by estrogen/ estrogen receptor α in breast cancer

Selvakumar Elangovan, Sabarish Ramachandran, Narayanan Venkatesan, Sudha Ananth, Jaya Pranava Gnana-Prakasam, Pamela Moore Martin, Darren D Browning, Patricia V Schoenlein, Puttur D Prasad, Vadivel Ganapathy, Muthusamy Thangaraju

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The NAD-dependent histone deacetylase silent information regulator 1 (SIRT1) is overexpressed and catalytically activated in a number of human cancers, but recent studies have actually suggested that it may function as a tumor suppressor and metastasis inhibitor in vivo. In breast cancer, SIRT1 stabilization has been suggested to contribute to the oncogenic potential of the estrogen receptor α (ERα), but SIRT1 activity has also been associated with ERα deacetylation and inactivation. In this study, we show that SIRT1 is critical for estrogen to promote breast cancer. ERα physically interacted and functionally cooperated with SIRT1 in breast cancer cells. ERα also bound to the promoter for SIRT1 and increased its transcription. SIRT1 expression induced by ERα was sufficient to activate antioxidant and prosurvival genes in breast cancer cells, such as catalase and glutathione peroxidase, and to inactivate tumor suppressor genes such as cyclin G2 (CCNG2) and p53. Moreover, SIRT1 inactivation eliminated estrogen/ERα- induced cell growth and tumor development, triggering apoptosis. Taken together, these results indicated that SIRT1 is required for estrogen-induced breast cancer growth. Our findings imply that the combination of SIRT1 inhibitors and antiestrogen compounds may offer more effective treatment strategies for breast cancer.

Original languageEnglish (US)
Pages (from-to)6654-6664
Number of pages11
JournalCancer Research
Volume71
Issue number21
DOIs
StatePublished - Nov 1 2011

Fingerprint

Estrogen Receptors
Estrogens
Breast Neoplasms
Cyclin G2
Neoplasms
Histone Deacetylases
Estrogen Receptor Modulators
Glutathione Peroxidase
Tumor Suppressor Genes
Growth and Development
NAD
Catalase
Antioxidants
Apoptosis
Neoplasm Metastasis
Growth
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

SIRT1 is essential for oncogenic signaling by estrogen/ estrogen receptor α in breast cancer. / Elangovan, Selvakumar; Ramachandran, Sabarish; Venkatesan, Narayanan; Ananth, Sudha; Gnana-Prakasam, Jaya Pranava; Martin, Pamela Moore; Browning, Darren D; Schoenlein, Patricia V; Prasad, Puttur D; Ganapathy, Vadivel; Thangaraju, Muthusamy.

In: Cancer Research, Vol. 71, No. 21, 01.11.2011, p. 6654-6664.

Research output: Contribution to journalArticle

Elangovan S, Ramachandran S, Venkatesan N, Ananth S, Gnana-Prakasam JP, Martin PM et al. SIRT1 is essential for oncogenic signaling by estrogen/ estrogen receptor α in breast cancer. Cancer Research. 2011 Nov 1;71(21):6654-6664. https://doi.org/10.1158/0008-5472.CAN-11-1446
Elangovan, Selvakumar ; Ramachandran, Sabarish ; Venkatesan, Narayanan ; Ananth, Sudha ; Gnana-Prakasam, Jaya Pranava ; Martin, Pamela Moore ; Browning, Darren D ; Schoenlein, Patricia V ; Prasad, Puttur D ; Ganapathy, Vadivel ; Thangaraju, Muthusamy. / SIRT1 is essential for oncogenic signaling by estrogen/ estrogen receptor α in breast cancer. In: Cancer Research. 2011 ; Vol. 71, No. 21. pp. 6654-6664.
@article{af3b7b01b254418d99beb9b0bf5afcd8,
title = "SIRT1 is essential for oncogenic signaling by estrogen/ estrogen receptor α in breast cancer",
abstract = "The NAD-dependent histone deacetylase silent information regulator 1 (SIRT1) is overexpressed and catalytically activated in a number of human cancers, but recent studies have actually suggested that it may function as a tumor suppressor and metastasis inhibitor in vivo. In breast cancer, SIRT1 stabilization has been suggested to contribute to the oncogenic potential of the estrogen receptor α (ERα), but SIRT1 activity has also been associated with ERα deacetylation and inactivation. In this study, we show that SIRT1 is critical for estrogen to promote breast cancer. ERα physically interacted and functionally cooperated with SIRT1 in breast cancer cells. ERα also bound to the promoter for SIRT1 and increased its transcription. SIRT1 expression induced by ERα was sufficient to activate antioxidant and prosurvival genes in breast cancer cells, such as catalase and glutathione peroxidase, and to inactivate tumor suppressor genes such as cyclin G2 (CCNG2) and p53. Moreover, SIRT1 inactivation eliminated estrogen/ERα- induced cell growth and tumor development, triggering apoptosis. Taken together, these results indicated that SIRT1 is required for estrogen-induced breast cancer growth. Our findings imply that the combination of SIRT1 inhibitors and antiestrogen compounds may offer more effective treatment strategies for breast cancer.",
author = "Selvakumar Elangovan and Sabarish Ramachandran and Narayanan Venkatesan and Sudha Ananth and Gnana-Prakasam, {Jaya Pranava} and Martin, {Pamela Moore} and Browning, {Darren D} and Schoenlein, {Patricia V} and Prasad, {Puttur D} and Vadivel Ganapathy and Muthusamy Thangaraju",
year = "2011",
month = "11",
day = "1",
doi = "10.1158/0008-5472.CAN-11-1446",
language = "English (US)",
volume = "71",
pages = "6654--6664",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "21",

}

TY - JOUR

T1 - SIRT1 is essential for oncogenic signaling by estrogen/ estrogen receptor α in breast cancer

AU - Elangovan, Selvakumar

AU - Ramachandran, Sabarish

AU - Venkatesan, Narayanan

AU - Ananth, Sudha

AU - Gnana-Prakasam, Jaya Pranava

AU - Martin, Pamela Moore

AU - Browning, Darren D

AU - Schoenlein, Patricia V

AU - Prasad, Puttur D

AU - Ganapathy, Vadivel

AU - Thangaraju, Muthusamy

PY - 2011/11/1

Y1 - 2011/11/1

N2 - The NAD-dependent histone deacetylase silent information regulator 1 (SIRT1) is overexpressed and catalytically activated in a number of human cancers, but recent studies have actually suggested that it may function as a tumor suppressor and metastasis inhibitor in vivo. In breast cancer, SIRT1 stabilization has been suggested to contribute to the oncogenic potential of the estrogen receptor α (ERα), but SIRT1 activity has also been associated with ERα deacetylation and inactivation. In this study, we show that SIRT1 is critical for estrogen to promote breast cancer. ERα physically interacted and functionally cooperated with SIRT1 in breast cancer cells. ERα also bound to the promoter for SIRT1 and increased its transcription. SIRT1 expression induced by ERα was sufficient to activate antioxidant and prosurvival genes in breast cancer cells, such as catalase and glutathione peroxidase, and to inactivate tumor suppressor genes such as cyclin G2 (CCNG2) and p53. Moreover, SIRT1 inactivation eliminated estrogen/ERα- induced cell growth and tumor development, triggering apoptosis. Taken together, these results indicated that SIRT1 is required for estrogen-induced breast cancer growth. Our findings imply that the combination of SIRT1 inhibitors and antiestrogen compounds may offer more effective treatment strategies for breast cancer.

AB - The NAD-dependent histone deacetylase silent information regulator 1 (SIRT1) is overexpressed and catalytically activated in a number of human cancers, but recent studies have actually suggested that it may function as a tumor suppressor and metastasis inhibitor in vivo. In breast cancer, SIRT1 stabilization has been suggested to contribute to the oncogenic potential of the estrogen receptor α (ERα), but SIRT1 activity has also been associated with ERα deacetylation and inactivation. In this study, we show that SIRT1 is critical for estrogen to promote breast cancer. ERα physically interacted and functionally cooperated with SIRT1 in breast cancer cells. ERα also bound to the promoter for SIRT1 and increased its transcription. SIRT1 expression induced by ERα was sufficient to activate antioxidant and prosurvival genes in breast cancer cells, such as catalase and glutathione peroxidase, and to inactivate tumor suppressor genes such as cyclin G2 (CCNG2) and p53. Moreover, SIRT1 inactivation eliminated estrogen/ERα- induced cell growth and tumor development, triggering apoptosis. Taken together, these results indicated that SIRT1 is required for estrogen-induced breast cancer growth. Our findings imply that the combination of SIRT1 inhibitors and antiestrogen compounds may offer more effective treatment strategies for breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=80155126751&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80155126751&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-11-1446

DO - 10.1158/0008-5472.CAN-11-1446

M3 - Article

VL - 71

SP - 6654

EP - 6664

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 21

ER -