Salem Kelley, Reese Rebecca M, Alarid Elaine T, Fowler Amy M
Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
McArdle Laboratory for Cancer Research, Department of Oncology and Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
J Endocr Soc. 2022 Dec 3;7(2):bvac186. doi: 10.1210/jendso/bvac186. eCollection 2022 Dec 15.
Positron emission tomography imaging with 2-deoxy-2-[F]-fluoro-D-glucose (FDG) is used clinically for initial staging, restaging, and assessing therapy response in breast cancer. Tumor FDG uptake in steroid hormone receptor-positive breast cancer and physiologic FDG uptake in normal breast tissue can be affected by hormonal factors such as menstrual cycle phase, menopausal status, and hormone replacement therapy.
The purpose of this study was to determine the role of the progesterone receptor (PR) in regulating glucose and FDG uptake in breast cancer cells.
PR-positive T47D breast cancer cells treated with PR agonists had increased FDG uptake compared with ethanol control. There was no significant change in FDG uptake in response to PR agonists in PR-negative MDA-MB-231 cells, MDA-MB-468 cells, or T47D PR knockout cells. Treatment of T47D cells with PR antagonists inhibited the effect of R5020 on FDG uptake. Using T47D cell lines that only express either the PR-A or the PR-B isoform, PR agonists increased FDG uptake in both cell types. Experiments using actinomycin D and cycloheximide demonstrated the requirement for both transcription and translation in PR regulation of FDG uptake. and mRNA expression and the enzymatic activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were increased after progestin treatment of T47D cells.
Thus, progesterone and progestins increase FDG uptake in T47D breast cancer cells through the classical action of PR as a ligand-activated transcription factor. Ligand-activated PR ultimately increases expression and activity of proteins involved in glucose uptake, glycolysis, and the pentose phosphate pathway.
使用2-脱氧-2-[F]-氟-D-葡萄糖（FDG）进行正电子发射断层扫描成像在临床上用于乳腺癌的初始分期、再分期以及评估治疗反应。激素因素，如月经周期阶段、绝经状态和激素替代疗法，会影响激素受体阳性乳腺癌中的肿瘤FDG摄取以及正常乳腺组织中的生理性FDG摄取。
本研究的目的是确定孕激素受体（PR）在调节乳腺癌细胞中葡萄糖和FDG摄取方面的作用。
与乙醇对照相比，用PR激动剂处理的PR阳性T47D乳腺癌细胞的FDG摄取增加。在PR阴性的MDA-MB-231细胞、MDA-MB-468细胞或T47D PR基因敲除细胞中，对PR激动剂的反应中FDG摄取没有显著变化。用PR拮抗剂处理T47D细胞可抑制R5020对FDG摄取的作用。使用仅表达PR-A或PR-B异构体的T47D细胞系，PR激动剂在两种细胞类型中均增加了FDG摄取。使用放线菌素D和环己酰亚胺的实验证明了PR调节FDG摄取中对转录和翻译的需求。孕激素处理T47D细胞后，葡萄糖-6-磷酸脱氢酶和6-磷酸葡萄糖酸脱氢酶的mRNA表达以及酶活性增加。
因此，孕酮和孕激素通过PR作为配体激活转录因子的经典作用增加T47D乳腺癌细胞中的FDG摄取。配体激活的PR最终增加参与葡萄糖摄取、糖酵解和磷酸戊糖途径的蛋白质的表达和活性。
