Lack of tumor suppression but induced loss of copies of indigenous chromosome 10 in vitro following microcell-mediated transfer of a deleted human der(9)t(X;9) chromosome to Syrian hamster BHK-191-5C cells.
We have previously shown that microcell-mediated transfer of a der(9)t(X;9) chromosome, containing an almost complete human chromosome (HSA) 9 derived from the human fibroblast strain GM0705, into the Syrian hamster (Mesocricetus auratus) cell line BHK-191-5C suppressed the anchorage independence and tumorigenicity of the hybrids. Transfer of a normal HSA X did not have any effect on these phenotypes. Although the recipient cell line contained a 1:1 ratio of near-diploid and near-tetraploid cells, all hybrids retaining the der(9) chromosome were near-tetraploid, in contrast to hybrids retaining a normal X chromosome. In the present study, we have generated microcell hybrids by transferring another der(9)t(X;9) chromosome derived from the human fibroblast strain GM01429. This derivative chromosome contained a deletion on the short arm of HSA 9 and was also missing the distal part of the long arm of HSA 9 due to the involvement in a reciprocal (constitutive) translocation of this chromosome with HSA X. Cytogenetic analysis showed that all hybrid clones were near-tetraploid, confirming our previous finding. We also observed that the introduction of the deleted der(9) chromosome forced the hybrids to lose Syrian hamster chromosome 10. A soft agar test and nude mice assay indicated that none of the hybrids was suppressed for either anchorage independent growth or tumor formation. These data suggest that there is an antagonistic relationship between growth-promoting genes and antiproliferative genes. The observed dosage effects of both growth-promoting and growth-suppressing genes indicate that cellular growth may be a quantitative trait.
Islam
M Q
MQ
Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden. quais@mcb.liu.se
Islam
K
K
D000818:Animals; D002455:Cell Division; D002459:Cell Fusion; D002460:Cell Line; D048429:Cell Size; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003260:Contact Inhibition; D006224:Cricetinae; D004261:DNA Replication / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism / Q000473:pathology; D007621:Karyotyping; D008647:Mesocricetus; D010641:Phenotype; D011123:Polyploidy; D013489:Suppression, Genetic / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*