GROWTH CONTROL OF MALIGNANT AND NORMAL KERATINOCYTES

本研究的目的是确定区分 鳞状细胞癌细胞（SqCC）的生长和分化 非肿瘤性角质形成细胞，在改变敏感性方面， 这些过程的生理调节剂，努力提供新的 抗癌治疗的靶点。 这一问题将由 利用表型异质性人SqCC细胞系 以及正常表皮细胞可以在限定的条件下体外培养， 生长和分化的条件和各种调节剂具有 被识别。 此外，手术标本的原代外植体 天然存在的SqCC和周围的非肿瘤上皮将 用于确认任何调查结果的一般性，并提供 体外生长和分化的特征作为 肿瘤的临床生物学 其次，转化表型（即异常表型）的遗传基础 调控生长和分化）的SqCC将探索， 利用DNA转染方法。 因此，选择的癌基因将是 转染到正常人角质形成细胞中，以绘制特异性 生长和分化的变化。 此外，还将尝试 用于检测SqCC基因组中的转化序列， 将这些肿瘤的基因组DNA转染到鼠角质形成细胞中， 使用SqCC的许多表型特征作为终点。

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.