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Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor α in T47D breast cancer cells

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Abstract

Potential interactions between prolactin (PRL) and estradiol (E2) in breast cancer cells were explored by examining the effect of PRL on estrogen receptor (ER) serine-118 phosphorylation, ER down-regulation, and E2-stimulated cell proliferation. Both E2 and PRL resulted in prolonged ERα serine-118 phosphorylation, but used different signaling pathways to achieve this end. Both hormones also decreased the amount of ERα, but the mechanisms were different: for E2, the decrease was rapid and resulted from proteasomic degradation, whereas for PRL the decrease was slow and resulted from an effect on levels of ERα mRNA. PRL alone had no effect on cell number, but enhanced the increase in number in response to E2. These results are the first to demonstrate similar effects of PRL and E2 on parameters considered key to E2’s effects. This suggests heretofore unrecognized and potentially important interactions between these two hormones in the natural history of breast cancer.

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Acknowledgments

This work was supported by a grant from the California Breast Cancer Research Program, 10PB-0127. Y.C. was a recipient of a Cancer Federation award during this period. K.H. was supported by an individual fellowship from the DOD Breast Cancer Research Program, BC0501103.

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  1. Division of Biomedical Sciences, University of California, Riverside, CA, 92521, USA

    YenHao Chen, KuangTzu Huang, KuanHui E. Chen & Ameae M. Walker

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  1. YenHao Chen
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Correspondence to Ameae M. Walker.

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Chen, Y., Huang, K., Chen, K.E. et al. Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor α in T47D breast cancer cells. Breast Cancer Res Treat 120, 369–377 (2010). https://doi.org/10.1007/s10549-009-0400-7

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