Estrogens and Progestins Cooperatively Shift Breast Cancer Cell Metabolism

Cancers

Ashley V. Ward¹  Duncan Riley¹  Jessica Finlay-Schultz¹  Shawna B. Matthews¹  Lynsey M. Fettig¹  Carol A. Sartorius¹  Paul S. MacLean²  Matthew Jackman²  Peter Kabos³  Kiran V. Paul³ 

[1] Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;

关键词: estrogens;    progestins;    estrogen receptor;    progesterone receptor;    breast cancer;    metabolism;   

DOI  :  10.3390/cancers14071776

来源: DOAJ

【 摘 要 】

Metabolic reprogramming remains largely understudied in relation to hormones in estrogen receptor (ER) and progesterone receptor (PR) positive breast cancer. In this study, we investigated how estrogens, progestins, or the combination, impact metabolism in three ER and PR positive breast cancer cell lines. We measured metabolites in the treated cells using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Top metabolic processes upregulated with each treatment involved glucose metabolism, including Warburg effect/glycolysis, gluconeogenesis, and the pentose phosphate pathway. RNA-sequencing and pathway analysis on two of the cell lines treated with the same hormones, found estrogens target oncogenes, such as MYC and PI3K/AKT/mTOR that control tumor metabolism, while progestins increased genes associated with fatty acid metabolism, and the estrogen/progestin combination additionally increased glycolysis. Phenotypic analysis of cell energy metabolism found that glycolysis was the primary hormonal target, particularly for the progestin and estrogen-progestin combination. Transmission electron microscopy found that, compared to vehicle, estrogens elongated mitochondria, which was reversed by co-treatment with progestins. Progestins promoted lipid storage both alone and in combination with estrogen. These findings highlight the shift in breast cancer cell metabolism to a more glycolytic and lipogenic phenotype in response to combination hormone treatment, which may contribute to a more metabolically adaptive state for cell survival.

【 授权许可】

Unknown