| OCR Text |
Show SURVIVIN EXPRESSION IN MELANOCYTES ENHANCES UV-INDUCED MELANOMA IN MICE )NORS Joshua Thomas, (Doug Grossman) Department of Biology Previously it has been shown that Survivin, an apoptosis inhibitor, is expressed in melanocytic nevi and melanoma, but not in normal melanocytes. Also, its inhibition in melanoma cells causes spontaneous apoptosis. To better understand the role of Survivin in melanoma pathogenesis, we examined the consequences of forced Survivin expression in melanocytes in vivo. Dct-Survivin mice were bred with melanoma-prone AAH19/HGF Tg mice. Progeny expressing either individual, neither or both (Survivin/HGF) transgenes were treated with 4000 J/m2 UV one day after birth and subsequently monitored for 43 wks. No tumors developed in non-Tg or singly Tg surviving mice. Median onset of pre-melanoma (focal) tumors was earlier (18 vs. 24 wks, p=.008) and overall tumor density was greater (7.7 vs. 5.2 tumors/mouse, p=.O4) in Survivin/HGF compared to HGF Tg mice. Histologic analysis also revealed a greater incidence of melanoma and higher rate of multiple primary melanomas in the Survivin/HGF cohort. Similar trends were seen for both Tg lines of Dct-Survivin mice. Finally, there was a greater rate of lymph node metastasis in Survivin/HGF mice with melanomas as compared to the HGF Tg mice. This study demonstrates that melanocyte expression of Survivin can enhance susceptibility to UV-induced melanoma formation in vivo. Joshua Thomas Dept. of Biology Faculty Sponsor Doug Grossman {125} |
