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

161 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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, 64(16), 5870-5875. https://doi.org/10.1158/0008-5472.CAN-04-0655