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Bicistronic vectors for animal models of breast and prostate cancer

The improving of our understanding of cancer development still depends
on cancer research at the molecular level. In his project, bigenic vectors for
animal models of breast and prostate cancer are created.
Bigenic constructs are useful because they create animals expressing two
genes of interest at a time, with one injection step and no need for crossings. In
order to produce these vectors, previous animal models have been analyzed, and
the elements that worked successfully in previous models were gathered in a new
arrangement for the creation of an improved model. In order to create a bigenic
vector, the viral internal ribosomal entry site was utilized, as a means of obtaining
two protein products from one transcript.
One vector, the MMTV-Neu1842-IRES-Cre was successful in generating
a line of transgenic mice. Female founders of this line already express the
expected phenotype, tumors of the mammary tissue. Once this line is established,
it can be crossed with the Rosa26 line, to determine the pattern of Cre expression.
Other vectors were created for models of prostate cancer, using the
probasin promoter and the MT oncogene. While transgenic mice were attempted,
there were no phenotype differences between wild type and transgenic mice.
All created vectors were tested for expression ofthe two genes carried in
tissue culture experiments. All the experiments were successful, indicating a
working oncogene (by means of a focus assay) and Cre activity (by excission
assay).
The new breast cancer animal model carrying the MMTV-Neu1842-IRESCre
construct is promising and can be used in combination with existing models
to answer some of the remaining questions regarding breast cancer signaling
pathways. / Thesis / Master of Science (MSc)

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22449
Date12 1900
CreatorsMorarescu, Diana
ContributorsMuller, W.J, Biology
Source SetsMcMaster University
Languageen_US
Detected LanguageEnglish
TypeThesis

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