Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells
- PMID: 25819032
- DOI: 10.1016/j.canlet.2015.03.030
Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells
Abstract
Ionizing radiation and cumulative exposure to steroid hormones are known risk factors for breast cancer. There is increasing evidence that breast tumors are driven by a subpopulation of tumor-initiating cancer stem cells (CSCs). In MCF10A non-cancerous basal-like PR(-) cells, progesterone treatment and X-rays generated ALDH(+) and CD44(+)/CD24(-) CSCs. Here, we report that in irradiated MCF10A cells, progesterone activated the PI3K/Akt pathway via membrane progesterone receptor (mPR). Inhibition of the PI3K/Akt pathway counteracted the generation of CSCs by progesterone and irradiation. The stimulation of PI3K/Akt via mPR resulted in the inactivation of FOXO transcriptional activity, the upregulation of snail and slug expression and a downregulation of miR-29 expression, which led to increased levels of KLF4, a transcription factor required for breast CSC maintenance. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs. This study provides a new mechanistic basis for progesterone and radiation-induced breast cancer risk in basal cells. In addition, the elucidation of new pathways and miRNA regulations involved in CSC generation and maintenance may open the door to potential novel anti-CSC strategies.
Keywords: Basal breast cancer; Cancer stem cells; Membrane progesterone receptor; Progesterone; Radiation; miRNA.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Similar articles
-
The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling.Life Sci. 2016 Oct 1;162:77-86. doi: 10.1016/j.lfs.2016.08.019. Epub 2016 Aug 26. Life Sci. 2016. PMID: 27569589
-
EB-virus latent membrane protein 1 potentiates the stemness of nasopharyngeal carcinoma via preferential activation of PI3K/AKT pathway by a positive feedback loop.Oncogene. 2016 Jun 30;35(26):3419-31. doi: 10.1038/onc.2015.402. Epub 2015 Nov 16. Oncogene. 2016. PMID: 26568302
-
Steroid hormones, steroid receptors, and breast cancer stem cells.J Mammary Gland Biol Neoplasia. 2015 Jun;20(1-2):39-50. doi: 10.1007/s10911-015-9340-5. Epub 2015 Aug 12. J Mammary Gland Biol Neoplasia. 2015. PMID: 26265122 Free PMC article. Review.
-
Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines.PLoS One. 2013 Oct 16;8(10):e77124. doi: 10.1371/journal.pone.0077124. eCollection 2013. PLoS One. 2013. PMID: 24146960 Free PMC article.
-
Role of KLF5 in hormonal signaling and breast cancer development.Vitam Horm. 2013;93:213-25. doi: 10.1016/B978-0-12-416673-8.00002-2. Vitam Horm. 2013. PMID: 23810009 Review.
Cited by
-
Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.Genes Dis. 2023 Jul 19;11(3):101043. doi: 10.1016/j.gendis.2023.05.024. eCollection 2024 May. Genes Dis. 2023. PMID: 38292177 Free PMC article. Review.
-
Expression and prognosis analysis of PAQR5 in kidney cancer.Front Oncol. 2022 Aug 31;12:955510. doi: 10.3389/fonc.2022.955510. eCollection 2022. Front Oncol. 2022. PMID: 36119517 Free PMC article.
-
Unexplored Functions of Sex Hormones in Glioblastoma Cancer Stem Cells.Endocrinology. 2022 Mar 1;163(3):bqac002. doi: 10.1210/endocr/bqac002. Endocrinology. 2022. PMID: 35023543 Free PMC article. Review.
-
Molecular mechanisms underlying the enhancement of carbon ion beam radiosensitivity of osteosarcoma cells by miR-29b.Am J Cancer Res. 2020 Dec 1;10(12):4357-4371. eCollection 2020. Am J Cancer Res. 2020. PMID: 33415004 Free PMC article.
-
Involvement of the Estrogen and Progesterone Axis in Cancer Stemness: Elucidating Molecular Mechanisms and Clinical Significance.Front Oncol. 2020 Sep 4;10:1657. doi: 10.3389/fonc.2020.01657. eCollection 2020. Front Oncol. 2020. PMID: 33014829 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous