Pgrmc1 (Progesterone Receptor Membrane Component 1) Associates with Epidermal Growth Factor Receptor and Regulates Erlotinib Sensitivity.
In: Journal of Biological Chemistry, Jg. 285 (2010-08-06), Heft 32, S. 24775-24782
academicJournal
Zugriff:
Tumorigenesis requires the concerted action of multiple pathways, including pathways that stimulate proliferation and metabolism. Epidermal growth factor receptor (EGFR) is transmembrane receptor-tyrosine kinase that is associated with cancer progression, and the EGFR inhibitors erlotinib/tarceva and tyrphostin/AG-1478 are potent anti-cancer therapeutics. Pgrmc1 (progesterone receptor membrane component 1) is cytochrome b5-related protein that is up-regulated in tumors and promotes cancer growth. Pgrmc1 and its homologues have been implicated in cell signaling, and we show here that Pgrmc1 increases susceptibility to AG-1478 and erlotinib, increases plasma membrane EGFR levels, and co-precipitates with EGFR. Pgrmc1 co-localizes with EGFR in cytoplasmic vesicles and co-fractionates with EGFR in high density microsomes. The findings have therapeutic potential because a Pgrmc1 small molecule ligand, which inhibits growth in a variety of cancer cell types, de-stabilized EGFR in multiple tumor cell lines. EGFR one of the most potent receptor-tyrosine kinases driving tumorigenesis, and our data support a role for Pgrmc1 in promoting several cancer phenotypes at least in part by binding EGFR and stabilizing plasma membrane pools of the receptor. [ABSTRACT FROM AUTHOR]
Titel: |
Pgrmc1 (Progesterone Receptor Membrane Component 1) Associates with Epidermal Growth Factor Receptor and Regulates Erlotinib Sensitivity.
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Autor/in / Beteiligte Person: | Ahmed, Ikhlas S. ; Rohe, Hannah J. ; Twist, Katherine E. ; Craven, Rolf J. |
Zeitschrift: | Journal of Biological Chemistry, Jg. 285 (2010-08-06), Heft 32, S. 24775-24782 |
Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.M110.134585 |
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