Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Dr. Ann Chambers

2nd Supervisor

Dr. Alan Tuck

Joint Supervisor

Abstract

The role of planar cell polarity (PCP) signalling in breast cancer is unclear, as evidence shows that activation of this pathway with WNT5A can either promote or inhibit progression. Using the 21T cells, which represent distinct stages of breast cancer progression when grown in a mouse xenograft model (21PT, atypical ductal hyperplasia; 21NT ductal carcinoma in situ; 21MT-1, invasive mammary carcinoma), I hypothesized that WNT5A will promote progression only when VANGL1, another component of PCP signalling, is elevated.

Each 21T cell line showed distinct stage-specific morphologies when grown in a Matrigel “on-top” assay. WNT5A overexpression promoted progression to an invasive phenotype in 21NT (ductal carcinoma in situ-like) cells that was partially dependent on RHOA, but not in 21PT (atypical ductal hyperplasia-like) cells. VANGL1 overexpression alone or with recombinant Wnt5a increased migration but had no effect on invasion in 21PT cells. Finally, knockdown of WNT5A and VANGL1 separately did not change morphology of 21MT-1 (invasive, metastatic) cells; however, WNT5A knockdown was incomplete.

PCP signalling likely plays a role in promoting progression to an invasive phenotype but this may be independent of high VANGL1 expression.


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