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Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1
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Diaz, J., Aranda, E., Henriquez, S., Quezada, M., Espinoza, E., Bravo, M. L., Oliva, B., Lange, S., Villalon, M., Jones, M., Brosens, Jan J., Kato, S., Cuello, M. A., Knutson, T. P., Lange, C. A., Leyton, L. and Owen, G. I. (2012) Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1. Journal of Endocrinology, Vol.214 (No.2). pp. 165-175. doi:10.1530/JOE-11-0310 ISSN 0022-0795.
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Official URL: http://dx.doi.org/10.1530/JOE-11-0310
Abstract
Progesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Journal of Endocrinology | ||||
| Publisher: | Society for Endocrinology | ||||
| ISSN: | 0022-0795 | ||||
| Official Date: | 2012 | ||||
| Dates: |
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| Volume: | Vol.214 | ||||
| Number: | No.2 | ||||
| Page Range: | pp. 165-175 | ||||
| DOI: | 10.1530/JOE-11-0310 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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