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Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer.
J Exp Clin Cancer Res. 2004 Sep; 23(3):385-94.JE

Abstract

The insulin-like growth factor I (IGF-I) receptor (IGF-IR) is a multifunctional transmembrane tyrosine kinase that has been implicated in neoplastic transformation. The tumorigenic potential of IGF-IR relies on its strong anti-apoptotic and mitogenic activity. The growth and survival signals of IGF-IR are mediated through multiple intracellular pathways, many of which emanate from insulin receptor substrate 1 (IRS-1). In hormone-dependent breast cancer cells, IGF-IR and IRS-1 are often co-expressed with the estrogen receptor alpha (ERalpha), and IGF-I and ER systems are engaged in a powerful functional cross-talk. Most notably, activation of ERalpha upregulates the expression of IRS-1, IGF-IR, and IGF-1, which results in amplification of IGF-I responses. Reciprocally, stimulation of IGF-IR increases the phosphorylation and activity of ERalpha. In contrast, in ERalpha-negative breast cancer cells and tumors, the levels of IGF-IR and IRS-1 are often decreased and IGF-I is non-mitogenic. Our data suggest that defective IGF-IR signaling in ERalpha-negative cells is related, at least in part, to improper activation of the IRS-1/PI-3K/Akt/GSK-3 pathway and lack of Rb1 phosphorylation. These defects are partially reversed by re-expression of ERalpha. Interestingly, some non-mitogenic IGF-I responses, such as migration and invasion are retained in the absence of ERalpha, suggesting that IGF-IR function in breast cancer cells might depend on the ERalpha status. The understanding of how ERalpha may dictate IGF-I responses will help in devising rational anti-IGF-IR strategies for breast cancer treatment.

Authors+Show Affiliations

Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. eva.surmacz@jefferson.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

15595626

Citation

Surmacz, E, and M Bartucci. "Role of Estrogen Receptor Alpha in Modulating IGF-I Receptor Signaling and Function in Breast Cancer." Journal of Experimental & Clinical Cancer Research : CR, vol. 23, no. 3, 2004, pp. 385-94.
Surmacz E, Bartucci M. Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer. J Exp Clin Cancer Res. 2004;23(3):385-94.
Surmacz, E., & Bartucci, M. (2004). Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer. Journal of Experimental & Clinical Cancer Research : CR, 23(3), 385-94.
Surmacz E, Bartucci M. Role of Estrogen Receptor Alpha in Modulating IGF-I Receptor Signaling and Function in Breast Cancer. J Exp Clin Cancer Res. 2004;23(3):385-94. PubMed PMID: 15595626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer. AU - Surmacz,E, AU - Bartucci,M, PY - 2004/12/15/pubmed PY - 2005/4/19/medline PY - 2004/12/15/entrez SP - 385 EP - 94 JF - Journal of experimental & clinical cancer research : CR JO - J Exp Clin Cancer Res VL - 23 IS - 3 N2 - The insulin-like growth factor I (IGF-I) receptor (IGF-IR) is a multifunctional transmembrane tyrosine kinase that has been implicated in neoplastic transformation. The tumorigenic potential of IGF-IR relies on its strong anti-apoptotic and mitogenic activity. The growth and survival signals of IGF-IR are mediated through multiple intracellular pathways, many of which emanate from insulin receptor substrate 1 (IRS-1). In hormone-dependent breast cancer cells, IGF-IR and IRS-1 are often co-expressed with the estrogen receptor alpha (ERalpha), and IGF-I and ER systems are engaged in a powerful functional cross-talk. Most notably, activation of ERalpha upregulates the expression of IRS-1, IGF-IR, and IGF-1, which results in amplification of IGF-I responses. Reciprocally, stimulation of IGF-IR increases the phosphorylation and activity of ERalpha. In contrast, in ERalpha-negative breast cancer cells and tumors, the levels of IGF-IR and IRS-1 are often decreased and IGF-I is non-mitogenic. Our data suggest that defective IGF-IR signaling in ERalpha-negative cells is related, at least in part, to improper activation of the IRS-1/PI-3K/Akt/GSK-3 pathway and lack of Rb1 phosphorylation. These defects are partially reversed by re-expression of ERalpha. Interestingly, some non-mitogenic IGF-I responses, such as migration and invasion are retained in the absence of ERalpha, suggesting that IGF-IR function in breast cancer cells might depend on the ERalpha status. The understanding of how ERalpha may dictate IGF-I responses will help in devising rational anti-IGF-IR strategies for breast cancer treatment. SN - 0392-9078 UR - https://www.unboundmedicine.com/medline/citation/15595626/Role_of_estrogen_receptor_alpha_in_modulating_IGF_I_receptor_signaling_and_function_in_breast_cancer_ L2 - http://www.diseaseinfosearch.org/result/960 DB - PRIME DP - Unbound Medicine ER -