Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor - PubMed (original) (raw)
Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor
A Migliaccio et al. EMBO J. 1998.
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/p21(ras)/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 anti-progestins 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 co-transfection 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/p21(ras)/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.
Similar articles
- Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells.
Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E, Auricchio F. Migliaccio A, et al. EMBO J. 1996 Mar 15;15(6):1292-300. EMBO J. 1996. PMID: 8635462 Free PMC article. - MAP kinase/estrogen receptor cross-talk enhances estrogen-mediated signaling and tumor growth but does not confer tamoxifen resistance.
Atanaskova N, Keshamouni VG, Krueger JS, Schwartz JA, Miller F, Reddy KB. Atanaskova N, et al. Oncogene. 2002 Jun 6;21(25):4000-8. doi: 10.1038/sj.onc.1205506. Oncogene. 2002. PMID: 12037682 - Two domains of the progesterone receptor interact with the estrogen receptor and are required for progesterone activation of the c-Src/Erk pathway in mammalian cells.
Ballaré C, Uhrig M, Bechtold T, Sancho E, Di Domenico M, Migliaccio A, Auricchio F, Beato M. Ballaré C, et al. Mol Cell Biol. 2003 Mar;23(6):1994-2008. doi: 10.1128/MCB.23.6.1994-2008.2003. Mol Cell Biol. 2003. PMID: 12612073 Free PMC article. - Chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways.
Vicent GP, Ballaré C, Zaurin R, Saragüeta P, Beato M. Vicent GP, et al. Ann N Y Acad Sci. 2006 Nov;1089:59-72. doi: 10.1196/annals.1386.025. Ann N Y Acad Sci. 2006. PMID: 17261755 Review. - Inhibition of erbB receptor (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer.
Kurokawa H, Arteaga CL. Kurokawa H, et al. Clin Cancer Res. 2001 Dec;7(12 Suppl):4436s-4442s; discussion 4411s-4412s. Clin Cancer Res. 2001. PMID: 11916237 Review.
Cited by
- Progesterone modulates cell growth via integrin αvβ3-dependent pathway in progesterone receptor-negative MDA-MB-231 cells.
Tsai CC, Yang YN, Wang K, Chen YE, Chen YF, Yang JC, Li ZL, Huang HM, Pedersen JZ, Incerpi S, Lee SY, Lin HY, Whang-Peng J. Tsai CC, et al. Heliyon. 2024 Jul 2;10(13):e34006. doi: 10.1016/j.heliyon.2024.e34006. eCollection 2024 Jul 15. Heliyon. 2024. PMID: 39071644 Free PMC article. - Modular Hub Genes in DNA Microarray Suggest Potential Signaling Pathway Interconnectivity in Various Glioma Grades.
Orda MA, Fowler PMPT, Tayo LL. Orda MA, et al. Biology (Basel). 2024 Mar 23;13(4):206. doi: 10.3390/biology13040206. Biology (Basel). 2024. PMID: 38666818 Free PMC article. - Progesterone receptor potentiates macropinocytosis through CDC42 in pancreatic ductal adenocarcinoma.
Liao YN, Gai YZ, Qian LH, Pan H, Zhang YF, Li P, Guo Y, Li SX, Nie HZ. Liao YN, et al. Oncogenesis. 2024 Feb 29;13(1):10. doi: 10.1038/s41389-024-00512-7. Oncogenesis. 2024. PMID: 38424455 Free PMC article. - A progesterone derivative linked to a stable phospholipid activates breast cancer cell response without leaving the cell membrane.
Font-Mateu J, Sanllehí P, Sot J, Abad B, Mateos N, Torreno-Pina JA, Ferrari R, Wright RHG, Garcia-Parajo MF, Joglar J, Goñi FM, Beato M. Font-Mateu J, et al. Cell Mol Life Sci. 2024 Feb 22;81(1):98. doi: 10.1007/s00018-024-05116-3. Cell Mol Life Sci. 2024. PMID: 38386110 Free PMC article. - Sleep apnea syndrome associated with gonadal hormone imbalance (Review).
Cojocaru C, Cojocaru E, Pohaci-Antonesei LS, Pohaci-Antonesei CA, Dumitrache-Rujinski S. Cojocaru C, et al. Biomed Rep. 2023 Oct 25;19(6):101. doi: 10.3892/br.2023.1683. eCollection 2023 Dec. Biomed Rep. 2023. PMID: 38025832 Free PMC article. Review.
References
- J Biol Chem. 1990 Jan 25;265(3):1376-80 - PubMed
- EMBO J. 1990 May;9(5):1603-14 - PubMed
- Endocr Rev. 1990 May;11(2):266-301 - PubMed
- Methods Enzymol. 1991;201:362-70 - PubMed
- Science. 1991 Dec 13;254(5038):1636-9 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous