Biological and Biochemical Studies on Melanogenesis and M elanoma Cells

For the previous ten years, we have been studying intracellular transport of melanosoma1 proteins and their biological and biochemical functions in melanoma cells. Melanosoma1 proteins,tyrosinase, tyrosinase-related protein 1 (TYRP1) and TYRP2/DOPAchrome tautomerase (DCT), gp100/Pme117 are transported from the trans-Golgi network (TGN) to earlystage melanosomes via endosoma1 compartments. We suggest that Rab7 is involved in the vesicular transport of tyrosinase and TYRP1 and in the melanogenesis through the regulation of gp100/Pme117 maturation. TYRP1 and TYRP 2/DCT were shown to play an essential role in suppressing TYR-mediated cytotoxicity in melanocytic cells, possibly through interaction with TYR in melanosomes. We also studied apoptotic cell death of melanoma cells and death mediators. Among p53 family members, p51A (p63) induced apoptosis in both wild-type and mutant p53-expressing melanoma cells more significantly than p53 and 73β. Interferon(IFN) exerts anti-tumor activities possibly by regulating IFN-stimulated genes. Caspase-2 activation was commonly associated with induction of apoptosis in IFN一β一sensitive melanoma cells. The diacylglycero1 kinase (DGK) , expressed in several human melanoma cell lines but not in melanocytes, was a novel positive regulator of NF-KB, which suppresses TNF一α一induced melanoma cell apoptosis

Two Cases of Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients with Chronic Human Papillomavirus Infection

Increasing evidence has suggested that human papillomaviruses (HPVs) are linked to a large subset of numerous malignant tumors, including mucosal squamous cell carcinoma (SCC); however, its involvement in cutaneous SCC has not fully been elucidated. Cutaneous SCC is the second most common type of skin cancer and is increasing in frequency every year. Since we have no satisfactory treatment for advanced SCC, it is important to provide a definitive diagnosis and appropriate therapeutic intervention at an early stage. Here, we present two cases of SCC arising in immunosuppressed patients. In these cases, we suspected the association between SCC and HPV infection histopathologically and succeeded in proving the presence of high-risk type HPV by PCR analysis (HPV 14 in case 1 and HPV 23 and 38 in case 2). Although it is unclear whether HPV actually induced SCC in our cases, our cases showed rapid progression comparing to typical courses of actinic keratosis (AK)/SCC. SCC and AK are common diseases; in daily practice, dermatologists examine many patients with immunosuppression of various causes. We should apply increased oncological vigilance to these patients to prevent an aggressive course of SCC/AK