Technical challenges and limitations of current mouse models of ovarian cancer

<p>Abstract</p> <p>The development of genetically engineered models (GEM) of epithelial ovarian cancer (EOC) has been very successful, with well validated models representing high grade and low grade serous adenocarcinomas and endometrioid carcinoma (EC). Most of these models were...

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Main Authors: Garson Kenneth, Gamwell Lisa F, Pitre Elizabeth MG, Vanderhyden Barbara C
Format: Article
Language:English
Published: BMC 2012-11-01
Series:Journal of Ovarian Research
Subjects:
Online Access:http://www.ovarianresearch.com/content/5/1/39
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author Garson Kenneth
Gamwell Lisa F
Pitre Elizabeth MG
Vanderhyden Barbara C
author_facet Garson Kenneth
Gamwell Lisa F
Pitre Elizabeth MG
Vanderhyden Barbara C
author_sort Garson Kenneth
collection DOAJ
description <p>Abstract</p> <p>The development of genetically engineered models (GEM) of epithelial ovarian cancer (EOC) has been very successful, with well validated models representing high grade and low grade serous adenocarcinomas and endometrioid carcinoma (EC). Most of these models were developed using technologies intended to target the ovarian surface epithelium (OSE), the cell type long believed to be the origin of EOC. More recent evidence has highlighted what is likely a more prevalent role of the secretory cell of the fallopian tube in the ontogeny of EOC, however none of the GEM of EOC have demonstrated successful targeting of this important cell type.</p> <p>The precise technologies exploited to develop the existing GEM of EOC are varied and carry with them advantages and disadvantages. The use of tissue specific promoters to model disease has been very successful, but the lack of any truly specific OSE or oviductal secretory cell promoters makes the outcomes of these models quite unpredictable. Effecting genetic change by the administration of adenoviral vectors expressing <it>Cre</it> recombinase may alleviate the perceived need for tissue specific promoters, however the efficiencies of infection of different cell types is subject to numerous biological parameters that may lead to preferential targeting of certain cell populations.</p> <p>One important future avenue of GEM of EOC is the evaluation of the role of genetic modifiers. We have found that genetic background can lead to contrasting phenotypes in one model of ovarian cancer, and data from other laboratories have also hinted that the exact genetic background of the model may influence the resulting phenotype. The different genetic backgrounds may modify the biology of the tumors in a manner that will be relevant to human disease, but they may also be modifying parameters which impact the response of the host to the technologies employed to develop the model.</p>
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spelling doaj.art-e4ebd0a8587f41e3831b0a82ec6ba3852023-01-02T13:36:48ZengBMCJournal of Ovarian Research1757-22152012-11-01513910.1186/1757-2215-5-39Technical challenges and limitations of current mouse models of ovarian cancerGarson KennethGamwell Lisa FPitre Elizabeth MGVanderhyden Barbara C<p>Abstract</p> <p>The development of genetically engineered models (GEM) of epithelial ovarian cancer (EOC) has been very successful, with well validated models representing high grade and low grade serous adenocarcinomas and endometrioid carcinoma (EC). Most of these models were developed using technologies intended to target the ovarian surface epithelium (OSE), the cell type long believed to be the origin of EOC. More recent evidence has highlighted what is likely a more prevalent role of the secretory cell of the fallopian tube in the ontogeny of EOC, however none of the GEM of EOC have demonstrated successful targeting of this important cell type.</p> <p>The precise technologies exploited to develop the existing GEM of EOC are varied and carry with them advantages and disadvantages. The use of tissue specific promoters to model disease has been very successful, but the lack of any truly specific OSE or oviductal secretory cell promoters makes the outcomes of these models quite unpredictable. Effecting genetic change by the administration of adenoviral vectors expressing <it>Cre</it> recombinase may alleviate the perceived need for tissue specific promoters, however the efficiencies of infection of different cell types is subject to numerous biological parameters that may lead to preferential targeting of certain cell populations.</p> <p>One important future avenue of GEM of EOC is the evaluation of the role of genetic modifiers. We have found that genetic background can lead to contrasting phenotypes in one model of ovarian cancer, and data from other laboratories have also hinted that the exact genetic background of the model may influence the resulting phenotype. The different genetic backgrounds may modify the biology of the tumors in a manner that will be relevant to human disease, but they may also be modifying parameters which impact the response of the host to the technologies employed to develop the model.</p>http://www.ovarianresearch.com/content/5/1/39Ovarian cancerMouse modelsGenetically engineeredOvaryOviductOvarian surface epithelium
spellingShingle Garson Kenneth
Gamwell Lisa F
Pitre Elizabeth MG
Vanderhyden Barbara C
Technical challenges and limitations of current mouse models of ovarian cancer
Journal of Ovarian Research
Ovarian cancer
Mouse models
Genetically engineered
Ovary
Oviduct
Ovarian surface epithelium
title Technical challenges and limitations of current mouse models of ovarian cancer
title_full Technical challenges and limitations of current mouse models of ovarian cancer
title_fullStr Technical challenges and limitations of current mouse models of ovarian cancer
title_full_unstemmed Technical challenges and limitations of current mouse models of ovarian cancer
title_short Technical challenges and limitations of current mouse models of ovarian cancer
title_sort technical challenges and limitations of current mouse models of ovarian cancer
topic Ovarian cancer
Mouse models
Genetically engineered
Ovary
Oviduct
Ovarian surface epithelium
url http://www.ovarianresearch.com/content/5/1/39
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AT gamwelllisaf technicalchallengesandlimitationsofcurrentmousemodelsofovariancancer
AT pitreelizabethmg technicalchallengesandlimitationsofcurrentmousemodelsofovariancancer
AT vanderhydenbarbarac technicalchallengesandlimitationsofcurrentmousemodelsofovariancancer