title: 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.
authors.affiliation: Department of Pathology, University Hospital, Zürich, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Oberhuber
authors.forename: B
authors.initials: B
authors.lastname: Seliger
authors.forename: R
authors.initials: R
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017364:Collagenases / Q000096:biosynthesis; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D015870:Gene Expression; D011905:Genes, ras; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010641:Phenotype; D011230:Precancerous Conditions; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D008249:Protein-Lysine 6-Oxidase; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534280:Ctsl protein, rat; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1