Transfer of a normal human chromosome 11 suppresses tumorigenicity of some but not all tumor cell lines.
The complete suppression of tumorigenicity of a human cervical cancer cell (HeLa) and a Wilms' tumor cell line (G401) following the introduction via microcell fusion of a single chromosome t(X;11) has been demonstrated by Stanbridge and co-workers. To determine whether other tumor cell lines are suppressed by chromosome 11, we performed chromosome transfer experiments via microcell fusion into various human tumor cell lines, including a uterine cervical carcinoma (SiHa), a rhabdomyosarcoma (A204), a uterine endometrial carcinoma (HHUA), a renal cell carcinoma (YCR-1), and a rat ENU-induced nephroblastoma (ENU-T1). We first isolated a mouse A9 cell containing a single human chromosome 11 with integrated pSV2-neo plasmid DNA. Following microcell fusion of the neo-marked chromosome 11 with the various tumors mentioned above, we isolated clones that were resistant to G418 and performed karyotypic analyses and chromosomal in situ hybridization to ensure the transfer of the marked chromosome. Whereas the parental cells of each cell line were highly tumorigenic, SiHa and A204 microcell hybrid clones at early passages were nontumorigenic in nude mice and HHUA was moderately tumorigenic. On the other hand, YCR-1 and ENU-T1 microcell hybrid clones were still highly tumorigenic following the introduction of chromosome 11. Thus, the introduction of a normal chromosome 11 suppresses the tumorigenicity of some but not all tumors, suggesting that the function of the putative suppressor gene(s) on chromosome 11 is effective only in specific tumors.
Oshimura
M
M
Laboratory of Cytogenetics, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Kugoh
H
H
Koi
M
M
Shimizu
M
M
Yamada
H
H
Satoh
H
H
Barrett
J C
JC
D000818:Animals; D002459:Cell Fusion; D002880:Chromosomes, Human, Pair 11; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009368:Neoplasm Transplantation; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology*