Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin

Na Yin, Dan Wang, Hua Zhang, Xia Yi, Xiaojing Sun, Bin Shi, Huijian Wu, Ge Wu, Xinjuan Wang, Yongfeng Shang

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, an adipocyte-derived cytokine, elicits proliferative effects in some cell types and potentially stimulates the growth of mammary epithelium. Here we show that leptin induced time- and dose-dependent signal transducer and activator of transcription 3 (STAT3) phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 kinase activation in breast carcinoma cells. Blocking STAT3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation of MCF-7 cells, whereas blocking ERK1/2 activation by a specific ERK1/2 kinase inhibitor, U0126, did not result in any significant changes in leptin-induced cell proliferation. Our experiments also showed that one member of the p160 family of steroid receptor coactivators, steroid receptor coactivator (SRC)-1, but not glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), also functioned in gene transactivation in response to leptin treatment. Glutathione S-transferase pull-down experiments showed that SRC-1 physically interacted with the activation domain of STAT3 and that chromatin immunoprecipitation experiments detected the occupancy of SRC-1, but not GRIP1 or AIB1, on the promoter of STAT3 target genes. Our experiments collectively showed that SRC-1 is involved in STAT3 signaling pathway that is implicated in leptin-stimulated cell growth.

Original languageEnglish (US)
Pages (from-to)5870-5875
Number of pages6
JournalCancer Research
Volume64
Issue number16
DOIs
StatePublished - Aug 15 2004

Fingerprint

STAT3 Transcription Factor
Nuclear Receptor Coactivator 1
Leptin
Breast Neoplasms
Nuclear Receptor Coactivator 2
Growth
Mitogen-Activated Protein Kinase 3
Phosphorylation
Steroid Receptors
Chromatin Immunoprecipitation
Mitogen-Activated Protein Kinase 1
MCF-7 Cells
Glutathione Transferase
Adipocytes
Transcriptional Activation
Genes
Breast
Phosphotransferases
Epithelium
Obesity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin. / Yin, Na; Wang, Dan; Zhang, Hua; Yi, Xia; Sun, Xiaojing; Shi, Bin; Wu, Huijian; Wu, Ge; Wang, Xinjuan; Shang, Yongfeng.

In: Cancer Research, Vol. 64, No. 16, 15.08.2004, p. 5870-5875.

Research output: Contribution to journalArticle

Yin, N, Wang, D, Zhang, H, Yi, X, Sun, X, Shi, B, Wu, H, Wu, G, Wang, X & Shang, Y 2004, 'Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin', Cancer Research, vol. 64, no. 16, pp. 5870-5875. https://doi.org/10.1158/0008-5472.CAN-04-0655
Yin, Na ; Wang, Dan ; Zhang, Hua ; Yi, Xia ; Sun, Xiaojing ; Shi, Bin ; Wu, Huijian ; Wu, Ge ; Wang, Xinjuan ; Shang, Yongfeng. / Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin. In: Cancer Research. 2004 ; Vol. 64, No. 16. pp. 5870-5875.
@article{352aedb72af745ecb9b9121f7a9ac3e9,
title = "Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin",
abstract = "Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, an adipocyte-derived cytokine, elicits proliferative effects in some cell types and potentially stimulates the growth of mammary epithelium. Here we show that leptin induced time- and dose-dependent signal transducer and activator of transcription 3 (STAT3) phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 kinase activation in breast carcinoma cells. Blocking STAT3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation of MCF-7 cells, whereas blocking ERK1/2 activation by a specific ERK1/2 kinase inhibitor, U0126, did not result in any significant changes in leptin-induced cell proliferation. Our experiments also showed that one member of the p160 family of steroid receptor coactivators, steroid receptor coactivator (SRC)-1, but not glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), also functioned in gene transactivation in response to leptin treatment. Glutathione S-transferase pull-down experiments showed that SRC-1 physically interacted with the activation domain of STAT3 and that chromatin immunoprecipitation experiments detected the occupancy of SRC-1, but not GRIP1 or AIB1, on the promoter of STAT3 target genes. Our experiments collectively showed that SRC-1 is involved in STAT3 signaling pathway that is implicated in leptin-stimulated cell growth.",
author = "Na Yin and Dan Wang and Hua Zhang and Xia Yi and Xiaojing Sun and Bin Shi and Huijian Wu and Ge Wu and Xinjuan Wang and Yongfeng Shang",
year = "2004",
month = "8",
day = "15",
doi = "10.1158/0008-5472.CAN-04-0655",
language = "English (US)",
volume = "64",
pages = "5870--5875",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "16",

}

TY - JOUR

T1 - Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin

AU - Yin, Na

AU - Wang, Dan

AU - Zhang, Hua

AU - Yi, Xia

AU - Sun, Xiaojing

AU - Shi, Bin

AU - Wu, Huijian

AU - Wu, Ge

AU - Wang, Xinjuan

AU - Shang, Yongfeng

PY - 2004/8/15

Y1 - 2004/8/15

N2 - Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, an adipocyte-derived cytokine, elicits proliferative effects in some cell types and potentially stimulates the growth of mammary epithelium. Here we show that leptin induced time- and dose-dependent signal transducer and activator of transcription 3 (STAT3) phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 kinase activation in breast carcinoma cells. Blocking STAT3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation of MCF-7 cells, whereas blocking ERK1/2 activation by a specific ERK1/2 kinase inhibitor, U0126, did not result in any significant changes in leptin-induced cell proliferation. Our experiments also showed that one member of the p160 family of steroid receptor coactivators, steroid receptor coactivator (SRC)-1, but not glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), also functioned in gene transactivation in response to leptin treatment. Glutathione S-transferase pull-down experiments showed that SRC-1 physically interacted with the activation domain of STAT3 and that chromatin immunoprecipitation experiments detected the occupancy of SRC-1, but not GRIP1 or AIB1, on the promoter of STAT3 target genes. Our experiments collectively showed that SRC-1 is involved in STAT3 signaling pathway that is implicated in leptin-stimulated cell growth.

AB - Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, an adipocyte-derived cytokine, elicits proliferative effects in some cell types and potentially stimulates the growth of mammary epithelium. Here we show that leptin induced time- and dose-dependent signal transducer and activator of transcription 3 (STAT3) phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 kinase activation in breast carcinoma cells. Blocking STAT3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation of MCF-7 cells, whereas blocking ERK1/2 activation by a specific ERK1/2 kinase inhibitor, U0126, did not result in any significant changes in leptin-induced cell proliferation. Our experiments also showed that one member of the p160 family of steroid receptor coactivators, steroid receptor coactivator (SRC)-1, but not glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), also functioned in gene transactivation in response to leptin treatment. Glutathione S-transferase pull-down experiments showed that SRC-1 physically interacted with the activation domain of STAT3 and that chromatin immunoprecipitation experiments detected the occupancy of SRC-1, but not GRIP1 or AIB1, on the promoter of STAT3 target genes. Our experiments collectively showed that SRC-1 is involved in STAT3 signaling pathway that is implicated in leptin-stimulated cell growth.

UR - http://www.scopus.com/inward/record.url?scp=4143118039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4143118039&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-0655

DO - 10.1158/0008-5472.CAN-04-0655

M3 - Article

C2 - 15313931

AN - SCOPUS:4143118039

VL - 64

SP - 5870

EP - 5875

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 16

ER -