Document Type

Dissertation

Date of Award

6-2024

School/College

College of Pharmacy and Health Sciences (COPHS)

Degree Name

Ph.D. in Pharmaceutical Science

Committee Chairperson

Yun Zhang, Ph.D.

Committee Member 1

Ya Fatou Njie Mbye, Ph.D.

Committee Member 2

Ya Fatou Njie Mbye, Ph.D.

Committee Member 3

Omonike Olaleye, Ph.D.

Committee Member 4

Audrey Player, Ph.D.

Committee Member 5

Bin Liu

Abstract

Breast cancer (BC) incidence increases with age, and a substantial proportion of aggressive forms of BC are observed in older women. The mechanisms underlying BC's age dependence remain unclear. Genetic alterations in BC most frequently occur in the tumor suppressor gene p53, with most mutations occurring somatically at arginine (R) 248 to tryptophan (W) or glutamine (Q) (R248W/Q in humans, corresponding to R245W/Q in mice) mutation. Previously, a conditional mouse p53wmR245W allele was generated. It allowed inducing p53R245W mutant in the mammary epithelium of the p53wmR245W/+ mice by delivering adenovirus expressing Cre (Ad-Cre) into the mammary ducts, leading to metastatic mammary tumor development. This study aims to utilize this model to assess the differences between the mammary tumors driven by p53R245W mutant induced in 2-month (corresponding to a human age of ~20 years old) and 10-month-old (corresponding to a human age of ~50 years old) female mice and investigate the underlying mechanism.

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