TERMINAL DIFFERENTIATION OF EPIDERMAL AND ADIPOSE CELLS

这项工作致力于在两种简单的培养条件下进行研究 哺乳动物细胞类型的分化：1)人类表皮细胞及其 近亲为其他复层鳞状上皮的角质形成细胞； 这种细胞类型经历了末端分化的程序，以产生 最后阶段类似于角质细胞和2)衍生的前脂肪细胞系 从3T3分化为脂肪细胞，并能分化为脂肪细胞。对两个人都是 我们的系统中有许多蛋白质是细胞的特征 其末端分化状态与相应的cDNAs和 基因组克隆。 我们计划研究从前体状态的转变，在这种状态下，细胞 能够长期增殖(人类角质形成细胞)或 无限增殖(3T3前体脂肪细胞)，向终末分化 不可能进一步分裂的状态。我们将研究 为了了解分化的特异性标记的出现 差异化计划是如何协调的。对于表皮细胞来说 我们将使用cdna和基因组克隆来获得总蛋白和几个 角蛋白；用于脂肪分化的甘油磷酸类似克隆 脱氢酶和两个未知的标记蛋白，分别为13和28kd。这 研究将包括对相应基因的结构进行分析， 维生素A对培养的表皮细胞分化的影响 (角蛋白合成和包膜交联的调节)，以及 生长激素促进卵巢癌细胞分化的研究进展 前体脂肪细胞。我们将尝试确定殖民地的属性 形成表皮细胞，以及这些特性在 肿瘤角质形成细胞。我们将研究IGF-1(即 生长激素诱导的多肽)对幼鼠克隆扩增的影响 分化脂肪细胞。这些研究可望阐明 分化通常如何导致细胞增殖停滞和 这种偶联的缺失是如何导致肿瘤的。

This work is devoted to the study under simple culture conditions of two differentiating mammalian cell types: 1) the human epidermal cell and its close relatives the keratinocytes of other stratified squamous epithelia; this cell type undergoes a program of terminal differentiation to produce a final stage resembling the corneocyte and 2) a preadipose cell line derived from 3T3 and able to differentiate terminally into adipocytes. For both systems we have a number of proteins that are characteristic of the cell in its terminally differentiated state, together with corresponding cDNA and genomic clones. We plan to examine the transition from precursor state, in which the cells are capable of either long term proliferation (human keratinocyte) or indefinite proliferation (3T3 preadipocyte), to a terminally differentiated state in which further division is impossible. We will examine the appearance of specific markers of differentiation in order to understand how the program of differentiation is coordinated. For the epidermal cell we will use cDNA and genomic clones for involucrin and several of the keratins; for adipose differentiation similar clones for glycerophosphate dehydrogenase and two unidentified marker proteins of 13 and 28 kd. This study will include an analysis of the structure of the corresponding genes, the effects of vitamin A on the differentiation of cultured epidermal cells (the regulation of keratin synthesis and of envelope cross-linking), and the effects of growth hormone in promoting the differentiation of preadipose cells. We will attempt to identify the properties of the colony forming epidermal cell, and the alteration of these properties in neoplastic keratinocytes. We will examine the possible role of IGF-1 (the growth hormone induced polypeptide) on clonal expansion of young differentiating adipose cells. These studies are expected to shed light on how differentiation normally leads to the arrest of cell mutiplication and how loss of this coupling leads to neoplasia.