Title

Spy1 role in mammary gland development and tumorigenesis

Date of Award

2007

Degree Type

Thesis

Department

Biological Sciences

Rights

CC BY-NC-ND 4.0

Abstract

Spy1 is a cell cycle activator, known to mediate cell cycle progression through an atypical activation of the cyclin dependent kinases. To understand the development and progression of breast cancer it is essential to elucidate the mechanisms and interactions of normal regulators of breast development. This study demonstrates that endogenous Spy1 protein and mRNA levels are tightly regulated during normal mammary gland development; being expressed during proliferative stages and downregulated at the onset of lactation. This appears to be regulated, in part, through the oncogene c-Myc and the MAPK signaling pathway. Importantly, we show that aberrant expression of the Spy1 protein prevents normal differentiation and results in disrupted morphology of the gland as well as tumorigenesis. Collectively this work has revealed a novel molecular mechanism regulating normal developmental processes in the breast and has provided evidence that the Spy1 protein may also be implicated in the development of breast cancer.