MECHANISMS OF REGULATION OF CELL PROLIFERATION

肽类生长因子对细胞增殖的刺激作用是 与快速转录激活一组特定的 称为“感受态”、“立即早期”或“早期反应”基因的基因。 至少这些基因中的一些蛋白质产物的改变 和/或调节它们的机制被认为是 这两个收购和转型的进展的核心 表型 这项研究将专门集中在一个监管 这些基因编码细胞骨架β-肌动蛋白，并将测试两个主要的 假设 第一，提出了负面监管的建议。 转录在调节β-肌动蛋白表达中起关键作用， 生长因子刺激细胞，其次，病变在阴性 控制机制负责改变β-肌动蛋白的模式， 在至少一种化学转化的细胞系中表达。 这些和 替代的可能性将通过描述顺式作用 调节元件和它们的同源蛋白，其介导 β-肌动蛋白基因对肽类生长因子的转录反应 在未转化的AKR-2B小鼠成纤维细胞和3-甲基胆蒽- 转化的克隆衍生物。 这些研究的结果将提供 深入了解肽生长因子 调节特定的基因表达，并可能提供相关的信息， 提出了多阶段致癌和肿瘤抑制的模型。

The stimulation of cell proliferation by peptide growth factors is associated with the rapid transcriptional activation of a specific set of genes termed "competence," "immediate-early," pr "early-response" genes. Alterations in the protein products of at least some of these genes and/or in the mechanisms by which they are regulated are believed to be central to both the acquisition and the progression of the transformed phenotype. This research will focus exclusively on the regulation of one such gene, that encoding cytoskeletal beta-actin, and will test two major hypotheses. First, it is proposed that negative regulation of transcription plays a key role in modulating beta-actin expression in growth factor stimulated cells, and secondly, that lesions in negative control mechanisms are responsible for altered patterns of beta-actin expression in at least one chemically-transformed cell line. These and alternate possibilities will be tested by delineating cis-acting regulatory elements and their cognate proteins which mediate the transcriptional response of the beta-actin gene to peptide growth factors in nontransformed AKR-2B mouse fibroblasts and in a 3-methylcholanthrene- transformed clonal derivative. The results of these studies will provide insight into the complex mechanisms by which peptide growth factors regulate specific gene expression and may provide information relevant to proposed models for multi-stage carcinogenesis and tumor suppression.