The glucocorticoid receptor mediates a survival signal in human mammary epithelial cells

Timothy J. Moran, Stacy Gray, Christina A. Mikosz, Suzanne D. Conzen

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Complex autocrine and paracrine signaling pathways control the multiple cycles of epithelial cell proliferation and involution characteristic of the human mammary gland. Activation of these pathways can lead to cell division, cell cycle arrest, apoptosis, or survival; their aberrant regulation often contributes to malignant transformation. In this report, we show that glucocorticoid signals a potent survival pathway in the immortalized human mammary epithelial cell line MCF10A. Withdrawal of glucocorticoid from defined media triggers apoptosis, despite the presence of epidermal growth factor and insulin. Apoptosis is accelerated by ectopic expression of c-Myc and blocked by overexpression of Bcl2. Although MCF10A cells can undergo apoptosis after CD95/Fas receptor activation, cell death caused by glucocorticoid withdrawal is independent of CD95/Fas receptor signaling. The mechanism through which glucocorticoid inhibits apoptosis is also independent of phosphatidylinositol 3-kinase activity and its downstream target Akt, thus establishing the existence of a novel epithelial cell survival pathway mediated by glucocorticoids.

Original languageEnglish (US)
Pages (from-to)867-872
Number of pages6
JournalCancer Research
Volume60
Issue number4
StatePublished - Feb 15 2000
Externally publishedYes

Fingerprint

Glucocorticoid Receptors
Glucocorticoids
Breast
Epithelial Cells
Apoptosis
Survival
CD95 Antigens
Autocrine Communication
Paracrine Communication
Phosphatidylinositol 3-Kinase
Human Mammary Glands
Cell Cycle Checkpoints
Epidermal Growth Factor
Cell Survival
Cell Cycle
Cell Death
Cell Proliferation
Insulin
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The glucocorticoid receptor mediates a survival signal in human mammary epithelial cells. / Moran, Timothy J.; Gray, Stacy; Mikosz, Christina A.; Conzen, Suzanne D.

In: Cancer Research, Vol. 60, No. 4, 15.02.2000, p. 867-872.

Research output: Contribution to journalArticle

Moran, Timothy J. ; Gray, Stacy ; Mikosz, Christina A. ; Conzen, Suzanne D. / The glucocorticoid receptor mediates a survival signal in human mammary epithelial cells. In: Cancer Research. 2000 ; Vol. 60, No. 4. pp. 867-872.
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