PATHOLOGY IN CELL CYCLE CONTROL OF DIFFERENTIATION

肿瘤转化的生物学机制已在 这个实验室导致的发展缺陷的综合 控制培养的间充质细胞中的细胞分化和增殖 干细胞 这些缺陷表现为无法监管 细胞分化和/或增殖在不同的状态， G1 细胞周期的阶段。 这一结论是由 对正常培养的干细胞和25个细胞克隆的研究， 选择它们是因为它们表达了一个或多个稳定的缺陷， 监管机制。 还已经确定， 癌发生选择性诱导分化控制缺陷， 培养的干细胞和增殖控制缺陷， 转变过程。 根据这些观察，我们开发了 这一模型表明，致癌作用的启动与 与表达异常分化控制和促进 癌发生与异常控制的表达有关， 细胞增殖 我们的研究旨在试图确定 调节细胞生长的生物化学和分子基础 正常干细胞的分化和发育 在癌变过程中的分化控制缺陷。 我们的研究是 也旨在建立这些发现对人类的相关性， 致癌作用 （N）个

The biological mechanisms of neoplastic transformation have been shown in this laboratory to result from the development of defects in the integrated control of cell differentiation and proliferation in cultured mesenchymal stem cells. These defects are expressed as the inability to regulate cellular differentiation and/or proliferation at distinct states in the G1 phase of the cell cycle. This conclusion has been established by studies on normal cultured stem cells and on 25 cell clones that were selected because they express one or more stable defects in these regulatory mechanisms. It has also been determined that an initiator of carcinogenesis selectively induces differentiation control defects in cultured stem cells and that proliferation control defects develop later in the transformation process. Based on these observations, we have developed a model that suggests that the initiation of carcinogenesis is associated with expression of aberrant differentiation control and that the promotion of carcinogenesis is associated with the expression of aberrant control of cellular proliferation. Our studies are designed to attempt to determine the biochemical and molecular basis for the regulation of cellular differentiation in normal stem cells and for the development of differentiation control defects during carcinogenesis. Our studies are also designed to establish the relevance of these discoveries to human carcinogenesis. (N)