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孕酮抑制乳腺癌细胞的侵袭和迁移，与它们的孕酮受体状态无关——一篇简短报告。

Progesterone suppresses the invasion and migration of breast cancer cells irrespective of their progesterone receptor status - a short report.

作者信息

Godbole Mukul, Tiwary Kanishka, Badwe Rajendra, Gupta Sudeep, Dutt Amit

机构信息

Integrated Genomics Laboratory, Advanced Centre for Treatment, Research and Education In Cancer, Tata Memorial Centre, Navi Mumbai, 410210, India.

Training School Complex, Homi Bhabha National Institute, Anushakti Nagar, Mumbai, India.

出版信息

Cell Oncol (Dordr). 2017 Aug;40(4):411-417. doi: 10.1007/s13402-017-0330-z. Epub 2017 Jun 26.

DOI:10.1007/s13402-017-0330-z
PMID:28653288
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5537311/
Abstract

PURPOSE

Pre-operative progesterone treatment of breast cancer has been shown to confer survival benefits to patients independent of their progesterone receptor (PR) status. The underlying mechanism and the question whether such an effect can also be observed in PR negative breast cancer cells remain to be resolved.

METHODS

We performed proteome profiling of PR-positive and PR-negative breast cancer cells in response to progesterone using a phospho-kinase array platform. Western blotting was used to validate the results. Cell-based phenotypic assays were conducted using PR-positive and PR-negative breast cancer cells to assess the effect of progesterone.

RESULTS

We found that progesterone induces de-phosphorylation of 12 out of 43 kinases tested, which are mostly involved in cellular invasion and migration regulation. Consistent with this observation, we found through cell-based phenotypic assays that progesterone inhibits the invasion and migration of breast cancer cells independent of their PR status.

CONCLUSION

Our results indicate that progesterone can inhibit breast cancer cell invasion and migration mediated by the de-phosphorylation of kinases. This inhibition appears to be independent of the PR status of the breast cancer cells. In a broader context, our study may provide a basis for an association between progesterone treatment and recurrence reduction in breast cancer patients, thereby providing a lead for modelling a randomized in vitro study.

摘要

目的

术前使用孕酮治疗乳腺癌已被证明可使患者获得生存益处，且与患者的孕酮受体（PR）状态无关。其潜在机制以及在PR阴性乳腺癌细胞中是否也能观察到这种效应的问题仍有待解决。

方法

我们使用磷酸激酶阵列平台对PR阳性和PR阴性乳腺癌细胞在孕酮作用下进行蛋白质组分析。采用蛋白质印迹法验证结果。使用PR阳性和PR阴性乳腺癌细胞进行基于细胞的表型分析，以评估孕酮的作用。

结果

我们发现，在所检测的43种激酶中，有12种激酶的磷酸化水平在孕酮作用下降低，这些激酶大多参与细胞侵袭和迁移的调控。与此观察结果一致，我们通过基于细胞的表型分析发现，孕酮可抑制乳腺癌细胞的侵袭和迁移，且与PR状态无关。

结论

我们的结果表明，孕酮可通过激酶的去磷酸化作用抑制乳腺癌细胞的侵袭和迁移。这种抑制作用似乎与乳腺癌细胞的PR状态无关。从更广泛的角度来看，我们的研究可能为孕酮治疗与乳腺癌患者复发率降低之间的关联提供依据，从而为开展随机体外研究提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4c/5537311/7582a772f8ec/13402_2017_330_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4c/5537311/c91062ed905a/13402_2017_330_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4c/5537311/f2d52086eb5d/13402_2017_330_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4c/5537311/7582a772f8ec/13402_2017_330_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4c/5537311/c91062ed905a/13402_2017_330_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4c/5537311/f2d52086eb5d/13402_2017_330_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4c/5537311/7582a772f8ec/13402_2017_330_Fig3_HTML.jpg

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