Role of chromosome 5 in immortalization and tumorigenesis of human keratinocytes.
Rhim et al. were first to show that superinfection of Ad12-SV40-infected immortalized human epidermal cells with an RNA tumor virus containing a ras oncogene, such as Ki-MSV, or their treatment with chemical carcinogens, leads to the ability of cells to both grow in anchorage-independent fashion and to form tumors in athymic nude mice. We describe details of the chromosome changes observed during the transformation. The culture was monitored through 40 passages after Ad12-SV40 infection. Chromosomes 9 and 11 showed random monosomy during the initial stages, but by passage 10 clonal evolution of the cell line was well established. Observed chromosome monosomy/trisomy coupled with chromosome rearrangements (identified as chromosomes A through F) were monosomy 13, loss of p arms of 8 and 10, partial loss of 5 (del(5)(q13) and of the q arm of 18(del(18)(q12)), and extra copies of 11q, 20 and 21. During its progression to tumorigenicity, a derived chromosome E containing a segment of 5q, also appeared to play a major role. The cells remained immortalized as long as the 5q segment was present in some of the cell population as derived chromosomes E or F. Derivative chromosome E showed noteworthy changes during the progression to tumorigenicity, in both viral and chemical transformations. There was loss of heterozygosity of 5q due to an exchange of 5q with chromosomes E or F. In Ki-MSV- and 4NQO-transformed cells, presence of an altered chromosome E (identified as E1) was observed. In MNNG-treated cells, there was a selection of population of cells with further alteration in chromosome E (identified as E3). Besides alterations in chromosome E, additional chromosome changes leading to gene activation and amplification indicating a multistep progression to tumorigenicity were observed. The cytogenetic data reiterate the ever-increasing need for molecular analysis of nonrandom karyotype changes.
Hukku
B
B
Children's Hospital of Michigan, Department of Pediatrics, Detroit 48201.
Rhim
J S
JS
D002273:Carcinogens; D002461:Cell Line, Transformed; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D006801:Humans; D007621:Karyotyping; D011003:Ploidies; D012867:Skin / Q000166:cytology
D002273:Carcinogens