Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cellular Oncology
Published in: Cellular Oncology 4/2017

Open Access 01-08-2017 | Report

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

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

Published in: Cellular Oncology | Issue 4/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
B. Weigelt, J.L. Peterse, L.J. van't Veer, Breast cancer metastasis: Markers and models. Nat Rev Cancer 5, 591–602 (2005)CrossRefPubMed
2.
R.W. Carlson and I.C. Henderson, Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole. Breast Cancer Res. Treat. 80 Suppl 1, S19–26; discussion S27–18 (2003)
3.
R. Badwe, R. Hawaldar, V. Parmar, M. Nadkarni, T. Shet, S. Desai, S. Gupta, R. Jalali, V. Vanmali, R. Dikshit, I. Mittra, Single-injection depot progesterone before surgery and survival in women with operable breast cancer: A randomized controlled trial. J Clin Oncol 29, 2845–2851 (2011)CrossRefPubMed
4.
O.J. Scully, B.-H. Bay, G. Yip, Y. Yu, Breast cancer metastasis. Cancer Genomics-Proteomics 9, 311–320 (2012)PubMed
5.
D. Wolczyk, M. Zaremba-Czogalla, A. Hryniewicz-Jankowska, R. Tabola, K. Grabowski, A.F. Sikorski, K. Augoff, TNF-alpha promotes breast cancer cell migration and enhances the concentration of membrane-associated proteases in lipid rafts. Cell Oncol 39, 353–363 (2016)CrossRef
6.
H. Mohammed, I.A. Russell, R. Stark, O.M. Rueda, T.E. Hickey, G.A. Tarulli, A.A. Serandour, S.N. Birrell, A. Bruna, A. Saadi, S. Menon, J. Hadfield, M. Pugh, G.V. Raj, G.D. Brown, C. D'Santos, J.L. Robinson, G. Silva, R. Launchbury, C.M. Perou, J. Stingl, C. Caldas, W.D. Tilley, J.S. Carroll, Progesterone receptor modulates ERalpha action in breast cancer. Nature 523, 313–317 (2015)CrossRefPubMedPubMedCentral
7.
H. Singhal, M.E. Greene, G. Tarulli, A.L. Zarnke, R.J. Bourgo, M. Laine, Y.F. Chang, S. Ma, A.G. Dembo, G.V. Raj, T.E. Hickey, W.D. Tilley, G.L. Greene, Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. Sci Adv 2, e1501924 (2016)CrossRefPubMedPubMedCentral
8.
H.C. Wang, W.S. Lee, Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration. Sci Rep 6 (2016)
9.
M. Dowsett, I.E. Smith, Presurgical progesterone in early breast cancer: So much for so little? J Clin Oncol 29, 2839–2841 (2011)CrossRefPubMed
10.
11.
Z. Yang, R. Bagheri-Yarmand, R.A. Wang, L. Adam, V.V. Papadimitrakopoulou, G.L. Clayman, A. El-Naggar, R. Lotan, C.J. Barnes, W.K. Hong, R. Kumar, The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa) suppresses c-Src and Pak1 pathways and invasiveness of human cancer cells. Clin Cancer Res 10, 658–667 (2004)CrossRefPubMed
12.
W. Li, Z. Liu, C. Zhao, L. Zhai, Binding of MMP-9-degraded fibronectin to beta6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer. Oncol Rep 34, 1345–1352 (2015)PubMed
13.
Y.J. Chen, K.N. Lin, L.M. Jhang, C.H. Huang, Y.C. Lee, L.S. Chang, Gallic acid abolishes the EGFR/Src/Akt/Erk-mediated expression of matrix metalloproteinase-9 in MCF-7 breast cancer cells. Chem Biol Interact 252, 131–140 (2016)CrossRefPubMed
14.
Z. Piperigkou, P. Bouris, M. Onisto, M. Franchi, D. Kletsas, A.D. Theocharis, N.K. Karamanos, Estrogen receptor beta modulates breast cancer cells functional properties, signaling and expression of matrix molecules. Matrix Biol 56, 4–23 (2016)CrossRefPubMed
15.
J. Kao, K. Salari, M. Bocanegra, Y.L. Choi, L. Girard, J. Gandhi, K.A. Kwei, T. Hernandez-Boussard, P. Wang, A.F. Gazdar, J.D. Minna, J.R. Pollack, Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One 4, e6146 (2009)CrossRefPubMedPubMedCentral
16.
J. Whyte, O. Bergin, A. Bianchi, S. McNally and F. Martin, Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development. Breast Cancer Res 11, 209 (2009)
17.
S. Dutta, C. Warshall, C. Bandyopadhyay, D. Dutta, B. Chandran, Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells. PLoS One 9, e97580 (2014)CrossRefPubMedPubMedCentral
18.
O.S. El-Masry, B.L. Brown, P.R. Dobson, Effects of activation of AMPK on human breast cancer cell lines with different genetic backgrounds. Oncol Lett 3, 224–228 (2012)PubMed
19.
C.C. Chen, D.B. Hardy, C.R. Mendelson, Progesterone receptor inhibits proliferation of human breast cancer cells via induction of MAPK phosphatase 1 (MKP-1/DUSP1). J Biol Chem 286, 43091–43102 (2011)CrossRefPubMedPubMedCentral
20.
J.T. Price, T. Tiganis, A. Agarwal, D. Djakiew, E.W. Thompson, Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3′-kinase and phospholipase C-dependent mechanism. Cancer Res 59, 5475–5478 (1999)PubMed
21.
G.S. Wu, Y.L. Song, Z.Q. Yin, J.J. Guo, S.P. Wang, W.W. Zhao, X.P. Chen, Q.W. Zhang, J.J. Lu, Y.T. Wang, Ganoderiol A-enriched extract suppresses migration and adhesion of MDA-MB-231 cells by inhibiting FAK-SRC-paxillin cascade pathway. PLoS One 8, e76620 (2013)CrossRefPubMedPubMedCentral
22.
M. Xie, S. You, Q. Chen, X. Chen, C. Hu, Progesterone inhibits the migration and invasion of A549 lung cancer cells through membrane progesterone receptor alpha-mediated mechanisms. Oncol Rep 29, 1873–1880 (2013)PubMed
23.
D. Kim, S. Kim, H. Koh, S.O. Yoon, A.S. Chung, K.S. Cho, J. Chung, Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J 15, 1953–1962 (2001)CrossRefPubMed
24.
K. Lei, L. Chen, E.X. Georgiou, S.R. Sooranna, S. Khanjani, J.J. Brosens, P.R. Bennett, M.R. Johnson, Progesterone acts via the nuclear glucocorticoid receptor to suppress IL-1beta-induced COX-2 expression in human term myometrial cells. PLoS One 7, e50167 (2012)CrossRefPubMedPubMedCentral
25.
M. Xie, L. Zhou, X. Chen, L.O. Gainey, J. Xiao, M.S. Nanes, A. Hou, S. You, Q. Chen, Progesterone and Src family inhibitor PP1 synergistically inhibit cell migration and invasion of human basal phenotype breast cancer cells. Biomed Res Int 2015, 426429 (2015)CrossRefPubMedPubMedCentral
26.
E.R. Fietz, C.R. Keenan, G. Lopez-Campos, Y. Tu, C.N. Johnstone, T. Harris, A.G. Stewart, Glucocorticoid resistance of migration and gene expression in a daughter MDA-MB-231 breast tumour cell line selected for high metastatic potential. Sci Rep 7, 43774 (2017)CrossRefPubMedPubMedCentral
27.
M.S. Fernandes, J.J. Brosens, B. Gellersen, Honey, we need to talk about the membrane progestin receptors. Steroids 73, 942–952 (2008)CrossRefPubMed
28.
C. Bellance, J.A. Khan, G. Meduri, A. Guiochon-Mantel, M. Lombes, H. Loosfelt, Progesterone receptor isoforms PRA and PRB differentially contribute to breast cancer cell migration through interaction with focal adhesion kinase complexes. Mol Biol Cell 24, 1363–1374 (2013)CrossRefPubMedPubMedCentral
29.
H. Seeger, D. Wallwiener, A.O. Mueck, The effect of progesterone and synthetic progestins on serum- and estradiol-stimulated proliferation of human breast cancer cells. Horm Metab Res 35, 76–80 (2003)CrossRefPubMed
Metadata
Title
Progesterone suppresses the invasion and migration of breast cancer cells irrespective of their progesterone receptor status - a short report
Authors
Mukul Godbole
Kanishka Tiwary
Rajendra Badwe
Sudeep Gupta
Amit Dutt
Publication date
01-08-2017
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 4/2017
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-017-0330-z

Other articles of this Issue 4/2017

Cellular Oncology 4/2017 Go to the issue

Original Paper

microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients

Original Paper

MDMX is a prognostic factor for non-small cell lung cancer and regulates its sensitivity to cisplatin

Original Paper

Association between epidermal growth factor receptor amplification and ADP-ribosylation factor 1 methylation in human glioblastoma

Original Paper

Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours

Original Paper

The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells

Report

Tumor cells interact with red blood cells via galectin-4 - a short report
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits