MECHANISMS OF REGULATION OF CELL PROLIFERATION

肽生长因子对细胞增殖的刺激作用 与一组特定基因的快速转录激活有关 被称为“能力”、“即刻-早期”、公关“早期反应”的基因。 这些基因中至少有一部分的蛋白质产物发生了变化 和/或监管它们的机制被认为是 对收购和转型的进展都至关重要 表型。这项研究将专门集中在对一种 这种编码细胞骨架β-肌动蛋白基因，将测试两个主要的 假设。第一，提出了负面监管的建议 转录在调控β-肌动蛋白表达中起关键作用 生长因子刺激细胞，其次是皮损呈阴性 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 另一种可能性将通过描绘顺位代理来测试 调节元件及其介导的同源蛋白 β-肌动蛋白基因对肽生长因子的转录反应 在未转化的AKR-2B小鼠成纤维细胞中和在3-甲基胆蒽中- 转化的克隆衍生品。这些研究的结果将提供 洞察多肽生长因子的复杂机制 调节特定基因的表达，并可能提供与 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.