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E2 + norethisterone promotes the PI3K-AKT pathway via PGRMC1 to induce breast cancer cell proliferation.
Climacteric. 2022 Feb 09 [Online ahead of print]C

Abstract

OBJECTIVE

This study aimed to find evidence that progesterone receptor membrane component 1 (PGRMC1) promotes estradiol (E2) + norethisterone (NET)-induced breast cancer proliferation through activation of the phosphatidylinositol-3-kinase (PI3K)-AKT pathway.

METHODS

PGRMC1-mediated breast cancer cellular proliferation and phosphorylation of PGRMC1 were studied using wild-type (hemagglutinin [HA]-tagged) MCF-7 cells, which were stably transfected with expression vector containing HA (MCF-7-HA cells), PGRMC1 (MCF-7-PGRMC1 cells) and Ser181 point mutated PGRMC1 (MCF-7-PGRMC1-S181A cells). Bioinformatics, cell proliferation, western blot, isobaric tags for relative and absolute quantitation (iTRAQ)-based RNA sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) and cell cycle in vitro assays were performed to indicate the function of PGRMC1 and its possible mechanisms in breast cancer.

RESULTS

NET + E2 elicited a significant proliferation in MCF-7-Vec at 10-6 M and 10-10 M, respectively. MCF-7-PGRMC1 did increase the phosphorylation of AKT or ERK, which can be blocked by treatment with casein kinase 2 (CK2) inhibitor quinalizarin or in MCF-7-PGRMC1-S181A cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the PI3K-AKT pathway is upregulated in MCF-7-PGRMC1 cells. Importantly, upregulation of the PI3K-AKT pathway mainly through promotion of cell cycle regulation strongly promoted cell proliferation in MCF-7-PGRMC1 cells.

CONCLUSIONS

CK2 is involved in phosphorylation of PGRMC1 at S181. The mechanism for the action of PGRMC1 for mediating proliferative progestogen effects obviously starts with promotion cell cycle regulation, and then activation of the PI3K-AKT pathway.

Authors+Show Affiliations

Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Department of Women's Health, University Women's Hospital and Research Center for Women's Health, University of Tuebingen, Tuebingen, Germany.Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Department of Women's Health, University Women's Hospital and Research Center for Women's Health, University of Tuebingen, Tuebingen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35137666

Citation

Zhang, L, et al. "E2 + Norethisterone Promotes the PI3K-AKT Pathway Via PGRMC1 to Induce Breast Cancer Cell Proliferation." Climacteric : the Journal of the International Menopause Society, 2022, pp. 1-9.
Zhang L, Ruan X, Gu M, et al. E2 + norethisterone promotes the PI3K-AKT pathway via PGRMC1 to induce breast cancer cell proliferation. Climacteric. 2022.
Zhang, L., Ruan, X., Gu, M., & Mueck, A. O. (2022). E2 + norethisterone promotes the PI3K-AKT pathway via PGRMC1 to induce breast cancer cell proliferation. Climacteric : the Journal of the International Menopause Society, 1-9. https://doi.org/10.1080/13697137.2022.2029837
Zhang L, et al. E2 + Norethisterone Promotes the PI3K-AKT Pathway Via PGRMC1 to Induce Breast Cancer Cell Proliferation. Climacteric. 2022 Feb 9;1-9. PubMed PMID: 35137666.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - E2 + norethisterone promotes the PI3K-AKT pathway via PGRMC1 to induce breast cancer cell proliferation. AU - Zhang,L, AU - Ruan,X, AU - Gu,M, AU - Mueck,A O, Y1 - 2022/02/09/ PY - 2022/2/9/entrez PY - 2022/2/10/pubmed PY - 2022/2/10/medline KW - Breast cancer KW - PGRMC1 KW - PI3K–AKT KW - phosphorylation SP - 1 EP - 9 JF - Climacteric : the journal of the International Menopause Society JO - Climacteric N2 - OBJECTIVE: This study aimed to find evidence that progesterone receptor membrane component 1 (PGRMC1) promotes estradiol (E2) + norethisterone (NET)-induced breast cancer proliferation through activation of the phosphatidylinositol-3-kinase (PI3K)-AKT pathway. METHODS: PGRMC1-mediated breast cancer cellular proliferation and phosphorylation of PGRMC1 were studied using wild-type (hemagglutinin [HA]-tagged) MCF-7 cells, which were stably transfected with expression vector containing HA (MCF-7-HA cells), PGRMC1 (MCF-7-PGRMC1 cells) and Ser181 point mutated PGRMC1 (MCF-7-PGRMC1-S181A cells). Bioinformatics, cell proliferation, western blot, isobaric tags for relative and absolute quantitation (iTRAQ)-based RNA sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) and cell cycle in vitro assays were performed to indicate the function of PGRMC1 and its possible mechanisms in breast cancer. RESULTS: NET + E2 elicited a significant proliferation in MCF-7-Vec at 10-6 M and 10-10 M, respectively. MCF-7-PGRMC1 did increase the phosphorylation of AKT or ERK, which can be blocked by treatment with casein kinase 2 (CK2) inhibitor quinalizarin or in MCF-7-PGRMC1-S181A cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the PI3K-AKT pathway is upregulated in MCF-7-PGRMC1 cells. Importantly, upregulation of the PI3K-AKT pathway mainly through promotion of cell cycle regulation strongly promoted cell proliferation in MCF-7-PGRMC1 cells. CONCLUSIONS: CK2 is involved in phosphorylation of PGRMC1 at S181. The mechanism for the action of PGRMC1 for mediating proliferative progestogen effects obviously starts with promotion cell cycle regulation, and then activation of the PI3K-AKT pathway. SN - 1473-0804 UR - https://www.unboundmedicine.com/medline/citation/35137666/E2_+_norethisterone_promotes_the_PI3K-AKT_pathway_via_PGRMC1_to_induce_breast_cancer_cell_proliferation. L2 - https://www.tandfonline.com/doi/full/10.1080/13697137.2022.2029837 DB - PRIME DP - Unbound Medicine ER -
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