Summary: | 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 of === Medicine, Department of === Experimental Medicine, Division of === Graduate
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