Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas.
Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas.
Am J Pathol. 2022 Feb;192(2):353-360. doi: 10.1016/j.ajpath.2021.10.008. Epub 2021 Nov 10.
Although the uterine cervix responds to the female sex hormone change, the role of progesterone in cervical cancer is poorly understood. It has been shown that medroxyprogesterone acetate (MPA) regresses cervical cancer in the transgenic mouse model expressing human papillomavirus type 16 E6 and E7 oncogenes. As MPA interacts most strongly with progesterone receptor (PR), we reasoned that PR would contribute to MPA-induced regression of cervical cancer. We also hypothesized that estrogen influences the therapeutic activity of MPA because it promotes cervical cancer growth in the same mouse model. The present study showed that the deletion of Pgr in the cervical cancer cells ablated the MPA's therapeutic effect in the human papillomavirus transgenic mouse model. Additionally, estrogen attenuated cancer regression by MPA in the same model system. These observations indicate that MPA can effectively regress cervical cancer only when cancer cells express PR and estrogen levels are low. These results suggest that, if translatable, MPA should be administered when estrogen levels are low in patients with PR-positive cervical cancer.
尽管子宫颈会对女性性激素变化做出反应，但孕激素在宫颈癌中的作用仍不清楚。已经表明，醋酸甲地孕酮（MPA）可使表达人乳头瘤病毒 16 型 E6 和 E7 致癌基因的转基因小鼠模型中的宫颈癌消退。由于 MPA 与孕激素受体（PR）的相互作用最强，我们推测 PR 将有助于 MPA 诱导的宫颈癌消退。我们还假设雌激素会影响 MPA 的治疗活性，因为它会促进同一小鼠模型中宫颈癌的生长。本研究表明，在宫颈癌细胞中删除 Pgr 可消除 MPA 在人乳头瘤病毒转基因小鼠模型中的治疗作用。此外，雌激素在同一模型系统中减弱了 MPA 对癌症的消退作用。这些观察结果表明，只有当癌细胞表达 PR 且雌激素水平较低时，MPA 才能有效地消退宫颈癌。这些结果表明，如果可以转化，那么在 PR 阳性宫颈癌患者的雌激素水平较低时，应该给予 MPA 治疗。
