久保, 宜明 Department of Dermatology, The University of Tokushima School of Medicine 徳島大学 教育研究者総覧 KAKEN研究者をさがす
村尾, 和俊 Department of Dermatology, The University of Tokushima School of Medicine 徳島大学 教育研究者総覧 KAKEN研究者をさがす
松本, 和也 Department of Plastic and Reconstructive Surgery, The University of Tokushima School of Medicine
squamous cell carcinomas (SCCs)
ultra-violet (UV) radiation
Squamous cell carcinomas (SCCs) of the skin were suggested to develop through a multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human skin keratinocytes. Exposure to ultra-violet (UV), especially UV-B, radiation is the most common cause for these genetic abnormalities in cells. We review causation of SCCs and genetic abnormalities in human SCCs with the current work. To elucidate the multistep process, we developed a method for examining the combinatorial function in vivo of plural genes in human keratinocytes. Using high efficiency retroviral transductions, we could express plural genes serially in normal human primary keratinocytes and use these cells to regenerate human skin on SCID mice. A combinatorial transduction of H-RasV12 and cyclin dependent kinase 4 (CDK4) produced human epidermal neoplasia resembling SCC. These findings were consistent with our previous results of mutation analysis in SCCs, one of which had both mutations of H-Ras gene and the INK4a locus. Therefore, it is suggested that a combination of these genetic abnormalities might be crucial to the carcinogenesis at least in a subset of SCCs.
The journal of medical investigation : JMI
jmi_49_3-4_111.pdf 88.2 KB