Year: 2019
Type: dissertation
Abstract: Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common p53 mutant in the pathogenesis and metastasis of prostate cancer. We found that Trp53R245W/- Pten-/- mice have invasive prostate cancer with complete penetrance and showed stable expression of the mutant p53. In addition, we found metastasis in Trp53R245W/- Pten-/- mice (3/15), which was absent in Trp53-/- Pten-/- mice (0/14). Analysis of metastasis also showed stable expression of the mutant p53. Taken together, these results indicate that p53R245W mutation has GOF in Pten-deficient prostate cancer.
Author: Ky Xuan Pham
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2973410942