Suppression of tumorigenicity in somatic cell hybrids

Abstract

Tumorigénicity assays of 48 intraspecies hybrids between human carcinoma-derived cells of the D98AH2 (HeLa) cell line and normal human diploid cells revealed that most are nontumorigenic in nude mice. Chromosome analysis revealed that these hybrids contained four chromosomes 11, presumably two from each parental cell. Their tumorigenic segregants sometimes, and their tumors always, had lost one or two copies of chromosome 11 (Klinger and Kaelbling, 1986). In this report we present evidence from analyses of DNA restriction fragment length polymorphic (RFLP) markers for the parental cell origin of the 11 which confirms that the four chromosomes 11 of the nontumorigenic hybrids consisted of two from each cell parent, and most notably, that one No. 11 of the diploid parental cell is always absent in cells of tumors that arise when the tumorigenic hybrids are injected into nude mice. We also found that both Nos. 11 of the D98 cells are identical at many RFLP sites on the short arm suggesting that loss of heterozygosity of the 11, or at least of the short arm of the 11, had occurred. Chromosome 11 of the diploid cells thus appears to carry alleles that suppress the tumorigenic potential of the D98 cells when present in two copies, but not in one. It remains to be seen if other chromosomes of the diploid cell effect suppression in concert with the 11.

The Genomic and Transcriptomic Landscape of a HeLa Cell Line

“…This indicates the presence of tumor suppressor genes on chromosome 11. LOH on this chromosome has also been observed in other cervical cancer cell lines (Stanbridge et al 1981; Kaelbling & Klinger 1986; Saxon et al 1986; Srivatsan et al 1986; Koi et al 1989). A potential cervical cancer-suppressor gene has been mapped to the 11q13 region (Srivatsan et al 2002), which in HeLa displays rearrangements symptomatic of chromothripsis (Figure 2).…”

Coinfection with viruses carrying the v-Ha-ras and v-myc oncogenes leads to growth factor independence by an indirect mechanism.

“…In summary, the results show that the growth factorindependent cells had significantly changed karyotypes. The apparent link in our experiments between the growth factor independence and gross karyotypic changes may result from the recessive nature of the tumorigenic phenotype (2,5,6,12). Unbalanced genomes caused by an abnormal distribution of chromosomes to the daughter cells after crisis may allow the expression of a recessive trait.…”