Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging

Autor:	Rebecca D. Dodd, Marion Vanneste, Michael B. Cohen, Patrick Breheny, Wade R. Gutierrez, James A. Brown, Michael D. Henry, Devon L. Moose, Nadine Bannick, Courtney Yong, Robert U. Svensson
Rok vydání:	2020
Předmět:	0301 basic medicine Male Carcinogenesis animal diseases Vimentin Optical Analysis medicine.disease_cause Biochemistry Metastasis Prostate cancer Mice 0302 clinical medicine Basic Cancer Research Medicine and Health Sciences Medicine Sequence Deletion Mice Knockout Multidisciplinary biology Prostate Cancer Genetically Modified Organisms Prostate Diseases Animal Models Prostatic Neoplasms Castration-Resistant Lymphatic system Oncology Experimental Organism Systems 030220 oncology & carcinogenesis Engineering and Technology Anatomy Genetic Engineering Research Article Biotechnology Epithelial-Mesenchymal Transition Imaging Techniques Science Urology Mouse Models Bioengineering Research and Analysis Methods 03 medical and health sciences Model Organisms Exocrine Glands Biomarkers Tumor PTEN Animals Epithelial–mesenchymal transition Chemical Characterization Monitoring Physiologic Genetically Modified Animals business.industry Bioluminescence Imaging PTEN Phosphohydrolase Cancers and Neoplasms Biology and Life Sciences Proteins medicine.disease Androgen receptor Mice Inbred C57BL Disease Models Animal Genitourinary Tract Tumors Cytoskeletal Proteins 030104 developmental biology Luminescent Measurements biology.protein Cancer research Animal Studies Prostate Gland Tumor Suppressor Protein p53 business
Zdroj:	PLoS ONE PLoS ONE, Vol 15, Iss 9, p e0232807 (2020)
ISSN:	1932-6203
Popis:	Here we have improved an existing mouse model of prostate cancer based on prostate-specific deletion of Pten and Trp53 by incorporating a Cre-activatable luciferase reporter. By coupling the deletion of those genes to the activation of a luciferase reporter, we were able to monitor tumor burden non-invasively over time. We show that, consistent with previous reports, deletion of both Pten and Trp53 on a C57BL/6 background accelerates tumor growth and results in both the loss of androgen receptor expression and castrate resistant tumors as compared with loss of Pten alone. Loss of Trp53 results in the development of sarcomatoid histology and the expression of markers of epithelial-to-mesenchymal transition Zeb1 and vimentin, with kinetics and penetrance dependent on whether one or both alleles of Trp53 were deleted. Homozygous deletion of Trp53 and Pten resulted in uniformly lethal disease by 25 weeks. While we were able to detect locally invasive disease in the peritoneal cavity in aggressive tumors from the double knockout mice, we were unable to detect lymphatic or hematogenous metastatic disease in lymph nodes or at distant sites.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0da90e83d689f3841a144a6d572090c3 https://pubmed.ncbi.nlm.nih.gov/32986721 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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