Partial restoration of pre‐transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants

Abstract

Neoplastic transformation mediated by ras oncogenes is associated with deregulated expression of genes encoding, for example, various proteases, lysyl oxidase, and smooth-muscle alpha-actin. To define the role of these genes in the initiation or maintenance of the ras-transformed state, we compared their steady-state mRNA levels in two different sets of preneoplastic fibroblast lines, ras-transformed clones, and phenotypic revertants derived from them. Compared with the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix metalloproteinase-3), and collagenase I (matrix metalloproteinase-1) mRNA but undetectable levels of lysyl oxidase mRNA. Partial restoration of lysyl oxidase transcription was observed in four of five phenotypic revertants derived from rat FE-8 and NIHpEJcl3 cells. The elevated levels of transin mRNA found in NIHpEJcl3 cells were diminished to the pretransformation level in interferon revertants but were not reduced in phenotypic rat FE-8 revertants expressing a high level of the ras oncoprotein. High steady-state levels of collagenase I mRNA were dependent on ras expression but were not closely associated with the transformed phenotype. High levels of cathepsin L mRNA were associated with neither high ras expression nor neoplastic transformation. The downregulation of smooth-muscle alpha-actin, characteristic of transformed cell lines, was not reversible in phenotypic revertants.