title: MUC1 positive, Kras and Pten driven mouse gynecologic tumors replicate human tumors and vary in survival and nuclear grade based on anatomical location.
abstract: Activating mutations of Kras oncogene and deletions of Pten tumor suppressor gene play important roles in cancers of the female genital tract. We developed here new preclinical models for gynecologic cancers, using conditional (Cre-loxP) mice with floxed genetic alterations in Kras and Pten. The triple transgenic mice, briefly called MUC1KrasPten, express human MUC1 antigen as self and carry a silent oncogenic KrasG12D and Pten deletion mutation. Injection of Cre-encoding adenovirus (AdCre) in the ovarian bursa, oviduct or uterus activates the floxed mutations and initiates ovarian, oviductal, and endometrial cancer, respectively. Anatomical site-specific Cre-loxP recombination throughout the genital tract of MUC1KrasPten mice leads to MUC1 positive genital tract tumors, and the development of these tumors is influenced by the anatomical environment. Endometrioid histology was consistently displayed in all tumors of the murine genital tract (ovaries, oviducts, and uterus). Tumors showed increased expression of MUC1 glycoprotein and triggered de novo antibodies in tumor bearing hosts, mimicking the immunobiology seen in patients. In contrast to the ovarian and endometrial tumors, oviductal tumors showed higher nuclear grade. Survival for oviduct tumors was significantly lower than for endometrial tumors (p = 0.0015), yet similar to survival for ovarian cancer. Oviducts seem to favor the development of high grade tumors, providing preclinical evidence in support of the postulated role of fallopian tubes as the originating site for high grade human ovarian tumors.
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Magee Women's Research Institute, Pittsburgh, Pennsylvania, United States of America.
authors: Tejas S
authors: TS
authors: Tirodkar
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Magee Women's Research Institute, Pittsburgh, Pennsylvania, United States of America.
authors: Raluca A
authors: RA
authors: Budiu
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Department of Pathology, Magee-Women's Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors: Esther
authors: E
authors: Elishaev
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Magee Women's Research Institute, Pittsburgh, Pennsylvania, United States of America.
authors: Lixin
authors: L
authors: Zhang
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Magee Women's Research Institute, Pittsburgh, Pennsylvania, United States of America.
authors: Jyothi T
authors: JT
authors: Mony
authors: Magee Women's Research Institute, Pittsburgh, Pennsylvania, United States of America.
authors: Joan
authors: J
authors: Brozick
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Magee Women's Research Institute, Pittsburgh, Pennsylvania, United States of America; Magee-Women's Hospital of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors: Robert P
authors: RP
authors: Edwards
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Magee Women's Research Institute, Pittsburgh, Pennsylvania, United States of America.
authors: Anda M
authors: AM
authors: Vlad
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000473:pathology*; D005260:Female; D011905:Genes, ras; D005833:Genital Neoplasms, Female / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D018396:Mucin-1 / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D059016:Tumor Microenvironment
chemical_list: D018396:Mucin-1; C577056:muc1 protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse