MOLECULAR GENETIC ANALYSIS OF FELINE CELLULAR GENES--A COMPARATIVE APPROACH

这些研究的目的是确定所需的生化事件 发生在肿瘤启动子-受体相互作用和激活之间 肿瘤转化的效应子。 候选第二信使 包括蛋白质磷酸化、活性氧产生和钙 动员。 蛋白激酶C（PKC）的激活和随后的 蛋白激酶C活性的丧失可能是在信号转导通路上， TPA促进的转化。 钙的药理学类似物， 镧系元素促进JB 6细胞恶性转化 PKC非依赖性通路。 镧系元素，如佛波醇酯，诱导 在（活化的）pro-1或pro-2转染的P-细胞中转化。 这 表明肿瘤启动子可以与激活的前基因合作， 通过PKC依赖性或 PKC非依赖性通路。 核蛋白15和16的合成 kd在P+细胞中是TPA可诱导的，但在P-细胞中不是，这一事件可以解释， 部分原因是P+细胞的促进敏感性。 最后，P+和P- 细胞在瞬时TPA刺激的病灶相关表达方面不同， 细胞P21 H-ras和肌动蛋白构型的不可逆变化， 这表明细胞骨架、细胞质和 核蛋白与原基因结合来转化。

The goal of these studies is to determine the required biochemical events that occur between tumor promoter-receptor interaction and the activation of effectors of neoplastic transformation. Candidate second messengers include protein phosphorylation, reactive oxygen generation, and calcium mobilization. Both activation of protein kinase C (PKC) and the subsequent loss of PKC activity may be on the signal transduction pathway for TPA-promoted transformation. Pharmacological analogs of calcium, the lanthanides promote neoplastic transformation in JB6 cells by a PKC-independent pathway. The lanthanides, like phorbol esters, induce transformation in (activated) pro-1 or pro-2-transfected P- cells. This indicates that tumor promoters can collaborate with activated pro genes to bring about neoplastic transformation by either PKC-dependent or PKC-independent pathways. The synthesis of nuclear proteins of 15 and 16 kd is TPA inducible in P+ but not in P- cells, an event that may account, in part, for the promotion sensitivity of P+ cells. Finally, P+ and P- cells differ in a transient, TPA-stimulated focus-associated expression of cellular P21 H-ras and an irreversible change in actin configuration, suggesting a possible collaboration of cytoskeletal, cytoplasmic and nuclear proteins with pro genes to bring about transformation.