Mowat M, Cheng A, Kimura N, Bernstein A, Benchimol S
Nature. 1985;314(6012):633-6. doi: 10.1038/314633a0.
There is now good evidence that the cellular protein, p53, is involved in the transformation process, although its precise role is unknown. It was reported recently that expression of the p53 gene can immortalize cells and that the p53 gene can replace the myc oncogene in a myc-ras immortalization/transformation assay. We have investigated whether p53 is involved in the progression towards the neoplastic state in vivo and report here that erythroleukaemic cell lines transformed by different isolates of Friend leukaemia virus show altered expression of the cellular p53 gene. High levels of p53 protein are found in certain lines, but the protein is undetectable in others. This heterogeneity in p53 gene expression is associated with heterogeneity in tumorigenicity. We demonstrate that genomic rearrangements are responsible for p53 gene inactivation in these cell lines and that they occur in vivo during the natural progression of Friend virus-induced erythroleukaemia.
现在有充分的证据表明，细胞蛋白p53参与了转化过程，尽管其确切作用尚不清楚。最近有报道称，p53基因的表达可使细胞永生化，并且在myc-ras永生化/转化试验中，p53基因可取代myc癌基因。我们研究了p53是否参与体内肿瘤状态的进展，并在此报告，由不同株系的弗氏白血病病毒转化的红白血病细胞系显示细胞p53基因表达发生改变。在某些细胞系中发现高水平的p53蛋白，但在其他细胞系中则检测不到该蛋白。p53基因表达的这种异质性与致瘤性的异质性相关。我们证明基因组重排是这些细胞系中p53基因失活的原因，并且它们发生在弗氏病毒诱导的红白血病自然进展过程中的体内。
