The autocrine-paracrine effects of IGF2 are important in the growth and differentiation of normal breast. In breast cancer (BC), IGF2 is initially stimulated by estrogen, progesterone and prolactin to regulate proliferation and cancer progression. These actions are mediated by the IGF-1R and insulin receptor A (IR-A) both members of the tyrosine- kinase receptors family. The activation of Estrogen Receptor (ER) is also very important in BC growth and progression. As BC progresses to estrogen-independent growth, the IGF-1R and the estrogen receptor (ER) interact in crosstalk mechanisms that are synergistic and results in enhanced activation of both receptors signaling cascades. This mechanism plays a central role in the transition of estrogen-dependent to estrogen-independent breast cancer (BC) progression. Basal-like BC (BLBC) is a sub-group of estrogen-independent tumors that have a very aggressive clinical behavior and are resistant to hormone-based therapy resulting in reduced disease-free survival period and increasing the mortality of breast cancer (BC) patients. Our BC research team has elucidated how IGF2 crosstalk signaling results in the activation of ER pathways independent of estrogen. Central to our investigation is how this mechanism is associated to the survival disparity observed among African American (AA) BC patients. BLBC accounts for nearly 15-20% of all breast cancers, however it represents 45% of all BC observed in AA patients. Analyses of subcellular compartments, Western-Blot and siRNA demonstrated that IGF2 activates ER-Î± and ER-Î² in ER negative BLBC cells Hs578t and CRL-2335. Our studies show that both IGF-1R and IR crosstalk with ER-Î± and ER-Î² promoting BLBC progression. This novel mechanism offers new therapeutic targets that will significantly impact treatment and diagnosis of BLBC patients.
Microbiology and Molecular Genetics
School of Medicine
De Leon, Daisy D.
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Estrogen; Breast Cancer;
Subject - Local
Estrogen receptors; Breast cancer cells
Loma Linda University Libraries
This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Richardson, Angelique, "IGF2 Promotes Activation of Estrogen Receptors in Basal-like Breast Cancer Cells" (2011). Loma Linda University Electronic Theses, Dissertations & Projects. 60.
Loma Linda University Electronic Theses & Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives