转化生长因子β_1及p53对大鼠气管上皮细胞转化的影响

Effect of TGF β_1, and p53 on the Transformation of Rat Tracheal Epithelial Cells

本义研究转化生长因子β1（TGF-β1）和P53对致癌物转化的大鼠气管上皮（RTE）细胞的影响。结果表明早期转化的RTE细胞（尚未具致癌性）和恶性转化的RTE细胞（已具致癌性）的条件培养基可以抑制原代RTE细胞的集落形成率（CFE），部分抑制早期转化RTE细胞的CFE，但对恶性转化的RTE细胞无抑制作用。TGF个；中和抗体可以阻断这种抑制作用，表明条件培养基中可能有TGF-β1。转化RTE细胞分泌TGF-β1可使对后者有抗性作用的细胞具有生长优势。为了评价P53对RTE细胞转化的作用，将野生型，突变型P53分别导人早期转化的RTE，研究表明，野生型P53抑制，而突变型P53促进转染细胞的CFE。突变型P53可能增强TGF-β1的分泌，从而促进转染细胞在裸鼠中癌变。本研究表明突变型P53可能通过TGF-β1自分泌或旁分泌途径促进RTE细胞恶性转化。

The present study was carried out to investigate the role of TGF 8, and p53 on carcinogen-transformed rat tracheal epithelial (RTE) cells. The results showed that the colony forming efficiency(CFE) of primary and early tranformed RTE cells (nontumorigenic) was inhibited or partialy inhibitedrespectively by the conditioned medium (CM) from early bosformed and malignant transfomed RTEcells (tumorigenic in nude mice). No such inhibition of CM on malignant transformed RTE wasobserved. The inhibition of CM was blocked by TGP β1, neutralized anibody, indicating the possiblepresence of TGF β1, in the CM. The secretion of TGF β1, produced by early and malignan transformedRTE cells may provide a selective advantage for the growth of transformed RTE cells which are resiboto TGF β1. In order to evalute the roIe of p53 during RTE transformation, wild or mUtant p53 wastransfected into early transformed RTE cells . It was observed that wild p53 could suppress and mutanip53 could increase CEF of the transfected cells. Mutan p53 probably increased TGF 6, secretion inCM, and enhanced malignant transformation of the transfected cells, when inoculated into nudemice. The results indicate that mutant p53 may promote tranformation of RTE cells through a TGFβ1, autocrine/paracrine pathway.