Suppression of tumorigenicity in somatic cell hybrids

Abstract

An analysis for cosegregation of chromosomes and tumorigenicity in 52 hybrids of human diploid × D98AH2 human carcinoma-derived cells reveals the consistent presence of four copies of chromosome 11 in all nontumorigenic hybrids (two from each of the parental cells) and a consistent loss of one or two copies of the 11 in all tumor cells derived from tumorigenic hybrids that grow in nude mice. In our earlier study, assays with restriction fragment length polymorphic (RFLP) markers for the cell parent origin of the chromosomes 11 in the hybrids indicated that at least one of the Nos. 11 lost in the tumor cells is from the diploid. Thus both Nos. 11 of the diploid seem to be required for complete and stable suppression of the tumorigenic phenotype. The results of the present study suggest that chromosome 2 may also carry suppressor information, but this causes only partial suppression of the tumorigenic phenotype in the absence of both Nos. 11. On the other hand, when the hybrids contain full complements of the 2 and the 11, suppression is very stable. All other chromosomes except for Nos. 1, 16, 17, 19, and 21 are clearly discordant with suppression. The latter chromosomes are not discordant often enough to allow their exclusion as possible carriers of suppressor information, particularly in the absence of RFLP evaluations. It is clear, however, that if they do carry such information it is not adequate for maintaining a stably suppressed phenotype in the absence of both Nos. 11 of the diploid.

Nonrandom duplication of the chromosome bearing a mutated Ha-ras-1 allele in mouse skin tumors.

“…A similar chromosome dosage dependency was observed in the suppression of tumorigenicity in hybrids derived from the human carcinoma cell line D98AH2 (29) and the fibrosarcoma cell line HT1080 (30). In the latter, the relative number of chromosome 1 alleles bearing the normal vs. activated N-ras gene was suggested to play a critical role in the suppression of tumorigenicity.…”

Normal human chromosome 2 induces cellular senescence in the human cervical carcinoma cell line SiHa

“…T h e presence of one or more tumor suppressor genes on human chromosome 2 was first suggested by Klinger and Kaelbling (1986). Their study revealed that tumorigenicity was suppressed in somatic cell hybrids between human cervical carcinoma cells (HeLa) and normal human fibroblasts, whereas the hybrids reexpressing tumorigenicity concomitantly lost chromosomes 2 and 1 1 derived from the normal cells.…”

Contributions of the Gordon‐Kosswig Melanoma System to the Present Concept of Neoplasia

“…Based on the observations of melanoma suppression by a particular chromosome, we proposed the appearance of human melanoma, retinoblastoma, Wilms' tumor, phaeochmmocytoma, and tumors of breast, ovaries, stomach, and colon many years ago as loss or impairment of tumor genespecific regulatory genes . Today, the formal similarity of the phenomenon of suppression or permission of tumorigenicity by a particular chromosome observable in the animals themselves, to that observable in human cell lines, e.g., chromosome 6 in melanoma, chromosome 11 in cervical carcinoma, W i l m s ' tumor, and fibrosarcoma, chromosome 17 in neuroblastoma and breast carcinoma, chromosome 18 and 5 in colorectal cancer (Stanbridge, 1976(Stanbridge, , 1989(Stanbridge, , 1990Klinger, 1982;Klinger and Kaelbling, 1986;Huff et al, 1988;Cropp et al, 1990;Dracopoli et al, 1985;Kugoh et al, 1990;Fearon et al, 1990;'hnaka et al, 1991;Weissmann et al, 1987; see reviews in Bock and Marsh, 1989), is self-evident and reveals formally a problem of gneral cancerology. Moreover, allele losses have recently been defined in human tumors by DNA studies of the site of the loss (Stanbridge, 1989; Ponder, Large interactive technical as well as living systems or parts of them, inherently evolve toward a critical state in which an obviously minor event, like incidental loss of a controlling element, can lead to a breakdown.…”