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Expression and regulation of Cyr61 in human breast cancer cell lines

Oncogene volume 21, pages 964–973 (2002)Cite this article

Abstract

We have shown that Cyr61, an angiogenic regulator, is overexpressed in invasive and metastatic human breast cancer cells and tumor biopsies. We have further demonstrated that Cyr61 promotes acquisition of estrogen-independence and anti-estrogen resistance in vivo in breast cancer cells. Moreover, we have demonstrated that Cyr61 induces tumor formation and tumor vascularization in vivo, events mediated through the activation of the MAPK and the Akt signaling pathways. Here we investigate how Cyr61 expression is regulated in both estrogen receptor (ER)-positive and ER-negative breast cancer cells. We demonstrate that Cyr61 mRNA and protein expression is inducible by estrogen and anti-estrogens in ER-positive breast cancer cells. We show that a labile protein as well as a negative regulator might be involved in Cyr61 expression in estrogen-dependent breast cancer cells. Other important regulators of Cyr61 expression in breast cancer cells that we found are the phorbol ester TPA, vitamin D, and retinoic acid. TPA causes positive regulation of Cyr61 expression in ER-positive MCF-7 cells. Vitamin D induces a transient stimulatory effect on Cyr61 gene expression. Lastly, retinoic acid has a negative effect on Cyr61 expression and downregulates its expression in MCF-7 cells. Interestingly, most of these effects are not seen in aggressive breast cancer cells that do not express ER and express high levels of Cyr61, such as the MDA-MB-231 cells. Our results are in agreement with our knowledge that Cyr61 promotes tumor growth, and that tumor-promoting agents have a positive impact on cells that express low levels of Cyr61, such as the ER-positive breast cancer cells; however, these agents have no significant effect on cells that express high levels of Cyr61. Our findings suggest an association between increased Cyr61 expression and an aggressive phenotype of breast cancer cells.

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Acknowledgements

The authors wish to thank Eddie Lo for technical assistance and Kevin Peet for editorial support. This work was supported by grants from the National Institutes of Health (DK49049), and from the Department of Energy (DE-AC03-76SF00098), and M-S Tsai was the recipient of a Breast Cancer Research Program Postdoctoral Traineeship from the Department of Defense.

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  1. Daphne F Bogart

    Present address: Bayer Corporation, 800 Dwight Way, Berkeley, 94710, California, CA, USA

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  1. Ernest Orlando Lawrence Berkeley National Laboratory, University of California, One Cyclotron Road, Berkeley, 94720, California, CA, USA

    Miaw-Sheue Tsai, Daphne F Bogart, Patricia Li, Inderjit Mehmi & Ruth Lupu

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Correspondence to Ruth Lupu.

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Tsai, MS., Bogart, D., Li, P. et al. Expression and regulation of Cyr61 in human breast cancer cell lines. Oncogene 21, 964–973 (2002). https://doi.org/10.1038/sj.onc.1205131

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