GROWTH CONTROL OF NORMAL AND MALIGNANT KERATINOCYTES

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The aim of this research is to define the features that distinguish the growth and differentiation of squamous carcinoma cells (SqCC) from those of non-neoplastic keratinocytes, in terms of altered sensitivities to physiological modulators of these processes, in an effort to provide new targets for anticancer treatment. This question shall be addressed by exploiting the fact that phenotypically heterogenous human SqCC cell lines as well as normal epidermal cells can be cultured in vitro under defined conditions and a variety of modulators of growth and differentiation have been identified. Moreover, primary explants of surgical specimens of naturally occurring SqCC's and surrounding non-neoplastic epithelium will be used to confirm the generality of any findings, as well as provide characteristics of in vitro growth and differentiation as corrollaries of the clinical biology of the tumors. Secondly, the genetic basis for the transformed phenotype (i.e. abnormal regulation of growth and differentiation) of SqCCs will be explored, by making use of DNA transfection methods. Thus, selected oncogenes will be transfected into normal human keratinocytes, in order to chart specific changes of growth and differentiation. In addition, an attempt will be made to detect transforming sequences in the genome of SqCCs by transfection of genomic DNA of these tumors into murine keratinocytes, using a number of phenotypic characteristics of SqCCs as end points.