Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy.
Melanoma is cancer of melanin-containing melanocyte cells. This neoplasm is one of the most deadly forms of skin cancer, and currently available therapeutic options are insufficient in significantly improve outcomes for many patients. Therefore, novel targets are required to effectively manage this neoplasm. Several sirtuins have previously been found to be upregulated in melanoma, so in this study, the expression profile of SIRT2 was determined. Employing a tissue microarray containing benign nevi, primary melanomas, and lymph node metastases, we have found that the tissue from lymph node metastases appears to have a significant upregulation of SIRT2 relative to primary tumors across the nuclear, cytoplasmic, and whole cell data. Additionally, SIRT2 staining was found to be higher in the nucleus of metastatic melanomas compared to cytoplasmic staining. As SIRT2 is considered to be a predominantly cytoplasmic protein, this is a novel and very interesting finding. This, combined with previous studies that show other sirtuins are increased in melanoma and involved in cellular proliferation and survival, leads to the suggestion that exploring pan-sirtuin inhibitors may be the best target for the next iteration of melanoma chemotherapeutics.
a Department of Dermatology , University of Wisconsin , Madison , WI , USA.
Melissa Jean
MJ
Wilking-Busch
a Department of Dermatology , University of Wisconsin , Madison , WI , USA.
Mary Ann
MA
Ndiaye
b Department of Pathology and Laboratory Medicine , University of Wisconsin , Madison , WI , USA.
Wei
W
Huang
a Department of Dermatology , University of Wisconsin , Madison , WI , USA.|c William S. Middleton VA Medical Center , Madison , WI , USA.
Nihal
N
Ahmad
D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics*; D009362:Neoplasm Metastasis; D056565:Sirtuin 2 / Q000378:metabolism*
D056565:Sirtuin 2
Cellular localization; Chemotherapy; Melanoma; SIRT2; Sirtuins; Skin