Medroxyprogesterone Acetate Prevention of Cervical Cancer through Progesterone Receptor in a Human Papillomavirus Transgenic Mouse Model

Abstract

Cervical dysplastic lesions called cervical intraepithelial neoplasias (CINs) need be treated to prevent cervical cancer. Currently available surgical procedures are effective, but the development of noninvasive treatment is warranted. In human papillomavirus transgenic mice engineered to express human papillomavirus type 16 E6 and E7, short-term treatment with 17b-estradiol induces CINs that progress to cervical cancer if the treatment is continued. In the present study, this mouse model was used to determine whether medroxyprogesterone acetate (MPA), a progestin drug, is chemopreventive. Human papillomavirus transgenic mice bearing CIN lesions were treated with MPA plus 17b-estradiol. Unlike control mice treated with 17b-estradiol alone, cervical cancer was absent in the MPA-treated mice. This observation suggests that MPA prevented CIN from progressing to invasive cancer. MPA was associated with inhibited cell proliferation and the promotion of apoptosis in CIN lesions. Confirming the role of the progesterone receptor, the preventive effect of MPA was absent in human papillomavirus transgenic mice in which the expression of progesterone receptor was genetically ablated. These results suggest that MPA is efficient in treating progesterone receptorepositive CIN lesions. These findings provide the basis for a biomarker-driven clinical trial of the secondary prevention of cervical cancer.

Combination of Estrogen Receptor Alpha and Histological Type Helps to Predict Lymph Node Metastasis in Patients with Stage IA2 to IIA2 Cervical Cancer

“…20,23 PR has also been reported to play a role in the prevention of cervical carcinogenesis in mice tests. 11,24 However, PR was not associated with LNM and survival in the current study, which may be because PR only functions in the early stage of carcinogenesis.…”

Microarray expression profiling of long noncoding RNAs in the progesterone‐treated lung cancer cells

“…10 In a human papillomavirus transgenic mouse model, medroxyprogesterone acetate prevented cervical dysplastic lesions from progressing to invasive cancer by inhibiting cell proliferation and promoting apoptosis. 11 P4 also inhibits the growth of pancreatic adenocarcinoma cells by modulating the expression of proliferation-related genes. 12 We previously demonstrated that expression of membrane progesterone receptor alpha (mPRα) was significantly down-regulated in breast cancer tissue of patients with tumor-metastasis-node (TMN) stage 4 disease compared to those at TNM 1-3.…”

“…P4 has been shown to interfere with the cell cycle of prostate stromal cells and suppress their proliferation, 9 cell migration and invasion 10 . In a human papillomavirus transgenic mouse model, medroxyprogesterone acetate prevented cervical dysplastic lesions from progressing to invasive cancer by inhibiting cell proliferation and promoting apoptosis 11 . P4 also inhibits the growth of pancreatic adenocarcinoma cells by modulating the expression of proliferation‐related genes 12 .…”