The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Enhanced Estrogen Receptor (ER) α, ERBB2, and MAPK Signal Transduction Pathways Operate during the Adaptation of MCF-7 Cells to Long Term Estrogen Deprivation
Open accessAbstract
The mechanisms involved in resistance to estrogen deprivation are of major importance for optimal patient therapy and the development of new drugs. Long term culture of MCF-7 cells in estrogen (E2)-depleted medium (long term estrogen deprivation; LTED) results in hypersensitivity to E2 coinciding with elevated levels of estrogen receptor (ER) alpha phosphorylated on Ser118 and MAPK, together with several of its downstream targets associated previously with ERalpha phosphorylation. Our data suggest elevated MAPK activity results from enhanced ERBB2 expression in the LTED cells versus the wild-type (wt), and treatment with the tyrosine kinase inhibitor ZD1839 revealed increased sensitivity in both transcription and proliferation assays. Similarly the MEK inhibitor U0126 decreased transcription and proliferation in the LTED cells and reduced their sensitivity to the proliferative effects of E2, while having no effect on the wt. However, the complete suppression of MAPK activity in the LTED cells did not inhibit ERalpha Ser118 phosphorylation suggesting that ER activity remained ligand-dependant. The LTED cells also expressed elevated levels of insulin-like growth factor-1R, and inhibition of phosphatidylinositol 3-kinase activity with LY294002 reduced basal ERalpha transactivation by 70% in the LTED cells compared with the wt. However, LY294002 had no effect on ERalpha Ser118 phosphorylation. These data suggest that although elevated levels of MAPK occur during LTED and influence the phenotype, this is unlikely to be the sole pathway operating to achieve adaptation.
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FGFR1 Amplification Drives Endocrine Therapy Resistance and Is a Therapeutic Target in Breast Cancer
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Metadata
- Authors
- Martin, L.-A., Farmer, I., Johnston, S. R. D., Ali, S., Marshall, C., & Dowsett, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 278
- Issue
- 33
- Pages
- 30458-30468
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2169988894
- Cited by
- 295
- References
- 47
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Martin, L.-A., Farmer, I., Johnston, S. R. D., Ali, S., Marshall, C., & Dowsett, M. (2003). Enhanced Estrogen Receptor (ER) α, ERBB2, and MAPK Signal Transduction Pathways Operate during the Adaptation of MCF-7 Cells to Long Term Estrogen Deprivation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m305226200
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