MEMBRANE PATHOLOGY IN CARCINOGENESIS

两个一般概念构成了我们研究 致癌作用 首先是调制的概念， 质膜蛋白的磷酸化在 肿瘤转化的过程。 这一概念得到了我们的支持。 最近的研究和对癌基因产物的研究，如pp60src. 第二个概念是，致癌作用是由基因缺陷引起的。 细胞增殖和分化的综合控制。 这个概念 我们最近的研究也支持了这一点， 造血细胞，并通过对感染病毒的细胞的研究， 表达逆转录病毒致癌基因产物。 我们的研究集中在实验上， 确定这两个过程如何在介导致癌作用中相互作用。 我们将建立如果调节质膜磷酸化 影响细胞增殖和分化的综合控制 在正常细胞中，然后确定是否开始致癌或 完全转变的结果是发展缺陷， 监管过程。 这些研究将使用“正常”间充质干细胞 细胞、起始间充质干细胞和间充质干细胞的克隆 感染了温度敏感致癌性禽肉瘤病毒的细胞。 我们的假设是，通过确定质膜是否以及如何 磷蛋白影响正常和肿瘤的综合控制 干细胞增殖和分化，我们将获得必要的 设计实验以建立这些机制的见解 磷蛋白介导致癌作用。 （一）

Two general concepts form the basis for our studies on the mechanisms of carcinogenesis. First is the concept that modulation in the phosphorylation of plasma membrane proteins serves a significant role in the process of neoplastic transformation. This concept is supported by our recent studies and by studies on oncogene products, such as pp60src. Second is the concept that carcinogenesis results from defects in the integrated control of cell proliferation and differentiation. This concept is also supported by our recent studies, by studies on normal and leukemic hematopoietic cells, and by studies on cells infected with viruses that express retroviral oncogene products. Our studies focus on experiments to determine how these two processes interface in mediating carcinogenesis. We will establish if modulation in plasma membrane phosphorylation influences the integrated control of cell proliferation and differentiation in normal cells and then determine if the initiation of carcinogenesis or complete transformation results from the development of defects in this regulatory process. These studies will employ "normal" mesenchymal stem cells, clones of initiated mesenchymal stem cells and mesenchymal stem cells infected with temperature-sensitive oncogenic avian sarcoma virus. It is our hypothesis that, by determining if and how plasma membrane phosphoproteins influence the integrated control of normal and neoplastic stem cell proliferation and differentiation, we will acquire the necessary insights to design experiments to establish the mechanism by which these phosphoproteins mediate carcinogenesis. (A)