Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Dale W Laird

Abstract

Connexins have been frequently identified as tumor suppressors in many cancers, however, their role in melanoma tumorigenesis remains controversial. Here, we show that B16-BL6 mouse melanoma cells express low levels of Cx26 and Cx43, rendering them gap junctional intercellular communication (GJIC) deficient. Following ectopic expression of Cx26 and Cx43, gap junction-like plaques were evident at the cell surface and the incidence of dye transfer was significantly increased similar to connexin-rich keratinocytes. The expression of Cx43, but not Cx26, significantly reduced proliferation and anchorage-independent growth relative to controls, whereas migration was unaffected. Additionally, Cx43-expressing melanoma cells displayed significantly reduced growth amongst keratinocytes, despite a complete lack of heterocellular GJIC. Furthermore, when grown in vivo in the chicken embryo, Cx43-expressing melanoma cells formed significantly smaller primary tumors compared to controls, whereas Cx26 expression did not alter primary tumor size. Collectively, these results suggest that Cx43, but not Cx26, acts as a tumor suppressor during melanoma tumorigenesis.

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