Caveolin-1 down-regulation activates estrogen receptor alpha expression and leads to 17β-estradiol-stimulated mammary tumorigenesis

Xintian Zhang, Peng Shen, Megan Coleman, Wei Zou, Brian W. Loggie, Leia M. Smith, ZhaoYi Wang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Constitutive activation of estrogen receptor alpha (ER-α) expression is an early event in breast cancer tumorigenesis. However, the mechanism whereby ER-α is constitutively activated during transformation of normal mammary cells has not been well established. Previously, we reported that haploinsufficiency of caveolin-1, a major structural protein that forms caveolae, resulted in anchorage-independent growth of a normal mammary epithelial cell line, MCF10A. Here, we further demonstrated that ER-α but not ER-β expression was constitutively activated in these caveolin-1 haploinsufficient cells. Transient treatment of MCF10A cells with β-methyl-cyclodextrin, a chemical that can displace caveolin-1 from the plasma membrane, also stimulated ER-α expression. We further found that the 17β-estradiol (E2) accelerated anchorage-independent growth of these cells in vitro and promoted their tumorigenesis in nude mice. These results suggest that dysregulation of caveolin-1 is one of the mechanisms by which ER-α expression is activated during initiation of breast tumorigenesis.

Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalAnticancer Research
Volume25
Issue number1 A
StatePublished - Jan 2005

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Caveolin 1
Estrogen Receptor alpha
Estradiol
Carcinogenesis
Breast
Down-Regulation
Haploinsufficiency
Caveolae
Cyclodextrins
Growth
Nude Mice
Epithelial Cells
Cell Membrane
Breast Neoplasms
Cell Line
Proteins

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Caveolin-1 down-regulation activates estrogen receptor alpha expression and leads to 17β-estradiol-stimulated mammary tumorigenesis. / Zhang, Xintian; Shen, Peng; Coleman, Megan; Zou, Wei; Loggie, Brian W.; Smith, Leia M.; Wang, ZhaoYi.

In: Anticancer Research, Vol. 25, No. 1 A, 01.2005, p. 369-375.

Research output: Contribution to journalArticle

Zhang, Xintian ; Shen, Peng ; Coleman, Megan ; Zou, Wei ; Loggie, Brian W. ; Smith, Leia M. ; Wang, ZhaoYi. / Caveolin-1 down-regulation activates estrogen receptor alpha expression and leads to 17β-estradiol-stimulated mammary tumorigenesis. In: Anticancer Research. 2005 ; Vol. 25, No. 1 A. pp. 369-375.
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