Date of Award
Master of Science
Dr. Dale W. Laird
Gap junction channels are assembled from connexins (Cx) and allow for intercellular communication. In our study, we characterized the role of Cx26 and Cx43 in three isogenic melanoma cell lines (FO, F10 and BL6) that vary in aggressiveness in mice. However, all three melanoma cell lines were shown to have similar levels of cell proliferation and anchorage-independent growth in soft agar, while the BL6 cells migrated significantly slower than FO and F10 cells. Cx26-based gap junctions were present in a subpopulation of all cell lines, while, Cx43 was localized to an intracellular compartment and only able to assemble into gap junction channels when E-cadherin was ectopically expressed. RNAi-based knockdown of Cx26 in BL6 cells showed a reduction in melanin levels and enhanced cell migration. Interestingly, BL6 cells with reduced Cx26 levels formed fewer microtumors in the 3D organotypic epidermis. All microtumors formed in the organotypic epidermis had a loss in Cx26 and Cx43 expression and remained isolated from the gap junction competent kératinocytes. Our results suggest that melanomas decrease connexins expression and are gap junction communication incompetent with each other and the surrounding kératinocytes. Thus, we proposed that the gap junction isolation in melanoma cells may allow for tumors to progress into more advance disease
Lee, Jack Yixian, "ROLE AND REGULATION OF Cx26 AND Cx43 IN MELANOMA" (2011). Digitized Theses. 3452.