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- Title
Activation of the Src/p21<sup>ras</sup>/Erk pathway by progesterone receptor via cross-talk with estrogen receptor.
- Authors
Migliaccio, Antimo; Piccolo, Domenico; Castoria, Gabriella; Di Domenico, Marina; Bilancio, Antonio; Lombardi, Maria; Gong, Wenrong; Beato, Miguel; Auricchio, Ferdinando
- Abstract
The molecular mechanisms by which ovarian hormones stimulate growth of breast tumors are unclear. It has been reported previously that estrogens activate the signal-transducing Src/p21ras/Erk pathway in human breast cancer cells via an interaction of estrogen receptor (ER) with c-Src. We now show that progestins stimulate human breast cancer T47D cell proliferation and induce a similar rapid and transient activation of the pathway which, surprisingly, is blocked not only by antiprogestins but also by anti-estrogens. In Cos-7 cells transfected with the B isoform of progesterone receptor (PRB), progestin activation of the MAP kinase pathway depends on cotransfection of ER. A transcriptionally inactive PRB mutant also activates the signaling pathway, demonstrating that this activity is independent of transcriptional effects. PRB does not interact with c-Src but associates via the N-terminal 168 amino acids with ER. This association is required for the signaling pathway activation by progestins. We propose that ER transmits to the Src/p21ras/Erk pathway signals received from the agonist-activated PRB. These findings reveal a hitherto unrecognized cross-talk between ovarian hormones which could be crucial for their growth-promoting effects on cancer cells.
- Publication
EMBO Journal, 1998, Vol 17, Issue 7, p2008
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/17.7.2008