التفاصيل البيبلوغرافية
| العنوان: |
Retinoic acid-induced growth arrest of MCF-7 cells involves the selective regulation of the IRS-1/PI 3-kinase/AKT pathway. |
| المؤلفون: |
del Rincon, Sonia V, Rousseau, Caroline, Samanta, Ratna, Miller, Wilson H |
| المصدر: |
Oncogene; 5/29/2003, Vol. 22 Issue 22, p3353, 8p |
| مصطلحات موضوعية: |
TRETINOIN, INSULIN-like growth factor-binding proteins, BREAST cancer, CANCER genetics, GENETICS |
| مستخلص: |
In the MCF-7 breast cancer cell line, insulin-like growth factors (IGFs) are known to elicit antiproliferative actions via the insulin receptor substrate-1 (IRS-1)/PI 3-kinase/AKT pathway. All-trans retinoic acid (RA) is a potent inhibitor of MCF-7 cell proliferation, but the mechanism by which growth regulation is achieved remains unclear. We investigated the effects of RA on the regulation of the IGF-IR and its key signaling elements: IRS-1, IRS-2, and SHC. Treatment of MCF-7 cells with RA caused a significant reduction in IRS-1 protein and tyrosine phosphorylation levels at a concentration and time consistent with RA-mediated growth inhibition. IRS-1 regulation is selective, as RA did not influence IRS-2 or SHC levels. Downstream signaling events were also selectively reduced, as RA abrogated IGF-I-stimulated AKT activation but did not alter erk1/2 activation. To confirm the importance of IRS-1 regulation by RA, we examined the response to RA in MCF-7 cells overexpressing IGF-IR and IRS-1. RA resistance was observed in MCF-7 cells overexpressing IRS-1 but not IGF-IR. This suggests that RA-mediated growth inhibition requires the selective downregulation of IRS-1 and AKT. Therapeutic agents targeting the IRS-1/PI 3-kinase/AKT pathway may enhance the cytostatic effects of RA in breast cancer, since overexpression of IRS-1 and AKT have been reported in primary breast tumors.Oncogene (2003) 22, 3353-3360. doi:10.1038/sj.onc.1206485 [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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