Date of Award

2011

Degree Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

First Advisor

Porter, Lisa (Biological Sciences)

Keywords

Biology, Genetics.

Rights

CC BY-NC-ND 4.0

Abstract

Speedy (Spy1A) is a novel cell cycle gene whose product binds to cyclin-dependent kinase-2 (CDK2) and activates its kinase activity to promote cell cycle progression through a cyclin independent mechanism. Spy1A is expressed naturally at high levels in the proliferating mammary gland, and aberrant overexpression of Spy1A results in precocious mammary development and eventually tumorigenesis in vivo. Induction of the mammary oncogene c-Myc upregulates Spy1A and I further demonstrate that Spy1A protein levels are elevated in mammary tissue and breast tumors derived from MMTV-Myc transgenic mice. Spy1A knockdown in F5A1-2 cell lines led to downregulation of cyclin-dependent kinase inhibitors (CKI) p21 and p27, a 23% reduction in proliferation rate, and a shift in cellular phenotype to a spindle-like/fibroblastic morphology. Together, findings support that Spy1A plays a functional role in mammary-related c-Myc signal transduction, and acts downstream of ER, c-Myc, and the MAPK cascade to regulate proliferation, mammary development, and carcinogenesis.

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