Role of tumor suppressor p33ING2 inhuman cutaneous melanoma

P33JNG2 was cloned through a homology search with p33INGlb, the founding member of ING family proteins in 1998. There have been several studies indicating that p331NG2 is a tumor suppressor candidate since it is involved in the regulation of transcription, apoptosis and senescence. People in our lab already revealed that p33ING2 plays an essential role in cellular stress response against UV irradiation (UVR) either by enhancing nucleotide excision repair (NER) or promoting apoptosis in melanoma cell line. So far, reduced ING family proteins have been reported in different tumor types including the loss of nuclear expression of p33INGlb in melanoma. Since p33ING2 is highly homologous to p331NGlb, we hypothesized that aberrant expression of p331NG2 may play a role in melanoma tumorigenesis. To test this hypothesis, we used tissue microarray (TMA) and immunohistochemistry to evaluate the expression pattern of p33ING2 in different stages of melanocyte lesions. We found that nuclear 1NG2 expression is significantly reduced in melanomas compared with dysplastic nevi. Moreover, there is no correlation between TNG2 nuclear expression and patient clinicopathological parameters or between 1NG2 nuclear expression and patient's 5-year survival in primary melanomas and metastatic melanomas. We then investigated if gene mutation is the reason for reduced ING2 nuclear expression in melanomas. Our results showed that no mutation is found in melanoma cell lines or melanoma tissue samples. At last, we restored the expression of p33TNG2 in melanomas by establishing the 1NG2 stable cell line, and cDNA microarray analysis was performed to identify the most abundantly induced or suppressed genes by overexpressed ING2 or UVR. We found that UVR can enhance expressions of two relatively new genes BTG2 and PLK3 while stably expression of p33ING2 significantly decreased RARRES1 (TIG1) expression.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat