title: Recurrence of cervical cancer and its resistance to progestin therapy in a mouse model.
abstract: Studies using K14E6/K14E7 transgenic mice expressing E6 and E7 oncoprotein of human papillomavirus type 16 (HPV16) have demonstrated that estrogen (E2) is required for the genesis and growth of cervical cancer. Our prior study using the same mouse model has showed that progestin drug medroxyprogesterone acetate (MPA) promotes regression of primary cervical cancer. In the present study, we use the same transgenic mouse model to determine whether the cancer recurs after MPA therapy. Cervical cancer recurred even if MPA treatment was continued. Unlike primary cervical cancer, the cancer recurred even in the absence of exogenous E2 when MPA treatment was ceased. Furthermore, recurrent cervical cancer did not fully regress upon MPA treatment. Our results support that MPA fails to completely eliminate primary cervical cancer cells and that remaining cancer cells grow independent of exogenous E2 and are refractory to MPA.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Fabiola F
authors.initials: FF
authors.lastname: Mehta
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Seunghan
authors.initials: S
authors.lastname: Baik
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Chung
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017211:Treatment Failure; D047368:Tumor Burden / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D018931:Antineoplastic Agents, Hormonal; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D017258:Medroxyprogesterone Acetate
keywords: cervical cancer; human papillomavirus (HPV); medroxyprogesterone acetate (MPA); recurrence; therapy resistance