Immortalization of conditionally transformed chicken cells: loss of normal p53 expression is an early step that is independent of cell transformation

• Published in: Genes & development Vol. 6; no. 5; pp. 876 - 887
• Main Authors: ULRICH, E, BOEHMELT, G, BIRD, A, BEUG, H
• Format: Journal Article
• Language: English
• Published: Cold Spring Harbor, NY Cold Spring Harbor Laboratory 01.05.1992
• Subjects: Animals; Base Sequence; Biological and medical sciences; Biotechnology; Blotting, Northern; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Viral - genetics; Chickens; Fundamental and applied biological sciences. Psychology; Gene Expression - genetics; Genes, p53 - genetics; Genes, Retinoblastoma - genetics; Molecular and cellular biology; Molecular Sequence Data; Mutation - genetics; Oncogenes - genetics; Polymerase Chain Reaction; Temperature; Vertebrata; Cell line; Animal; V-Onc gene; Chicken; Aves; Gene expression; Cell transformation; Fibroblast; Erythroblast; Temperature sensitive mutation; Tumor suppressor gene
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.6.5.876

Clones of mortal chicken fibroblasts and erythroblasts transformed by temperature-sensitive v-src and v-erb B oncoproteins have been developed into immortal cell lines that retain the conditional transformed phenotype. The expressions of two tumor suppressor genes, the retinoblastoma (Rb) gene and the p53 gene, were investigated during senescence, crisis, and cell line establishment. In temperature-sensitive (ts)-v-erb B erythroblasts and ts-v-src fibroblasts (as well as in v-myc macrophages), loss of p53 mRNA or expression of a mutated p53 gene invariably occurred in the early phase of immortalization. In contrast, expression of the Rb gene was unchanged at all stages of immortalization. Inactivation of the original temperature-sensitive oncogene led to loss of the transformed phenotype in fibroblasts and to differentiation in erythroblasts, even in lines that were immortal and lacked p53. The results demonstrate that the process of immortalization is distinct from cell transformation, probably requiring different mutational events.