Roles of tumour suppressor APAF-1 oncogenes ILK and Akt expression in human melanoma progression

The incidence of cutaneous malignant melanoma is increasing more rapidly than any other tumor. Malignant melanoma is a life-threatening skin cancer due to its highly metastatic characteristics and resistance to radio- and chemo-therapy. It is believed that the ability to evade apoptosis is the key mechanism for the rapid growth of cancer cells. However, the exact mechanism for failure in the apoptotic pathway in melanoma cells is unclear. In the current study, we used tissue microarray (TMA) and immunohistochemistry to evaluate the expression patterns of three apoptosis-related genes in melanocytic lesions, including the tumour suppressor Apaf-1, oncogenes integrin-linked kinase (ILK) and the activated form of Akt (phospho-Akt Ser-473). Our data showed that Apaf-l expression is significantly reduced in melanoma cells compared with normal nevi. We also found that in melanomas, strong ILK expression is significantly associated with tumour thickness. Strikingly, our TMA study on p-Akt indicated that strong p-Akt expression was associated with melanoma progression and invasion. Furthermore, strong p-Akt expression is inversely correlated with disease-specific 5-year survival of patients with primary melanoma. These data, coupled with a number of functional studies demonstrating an essential role of Akt activity in melanomagenesis, implicate that Akt signaling may serve as a promising therapeutic target for malignant melanoma.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat