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MUC1 positive, Kras and Pten driven mouse gynecologic tumors replicate human tumors and vary in survival and nuclear grade based on anatomical location

Tirodkar, TS and Budiu, RA and Elishaev, E and Zhang, L and Mony, JT and Brozick, J and Edwards, RP and Vlad, AM (2014) MUC1 positive, Kras and Pten driven mouse gynecologic tumors replicate human tumors and vary in survival and nuclear grade based on anatomical location. PLoS ONE, 9 (7).

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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. © 2014 Tirodkar et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tirodkar, TS
Budiu, RA
Elishaev, Eese9@pitt.eduESE9
Zhang, Lliz36@pitt.eduLIZ36
Mony, JT
Brozick, Jjeb197@pitt.eduJEB197
Edwards, RPrpe1@pitt.eduRPE10000-0003-0370-1390
Vlad, AManvst12@pitt.eduANVST12
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorElnitski, Laura L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Magee-Women's Research Institute
Date: 31 July 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0102409
Schools and Programs: School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
Refereed: Yes
Date Deposited: 24 Sep 2014 14:31
Last Modified: 03 Feb 2019 07:55
URI: http://d-scholarship.pitt.edu/id/eprint/22997

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