Inhibition of tumorigenicity of a murine squamous cell carcinoma (SCC) cell line by a putative tumor suppressor gene on human chromosome 7.
Alterations in oncogenes and tumor suppressor genes (TSG) are considered to be critical steps in oncogenesis. However information on putative TSG involved in the development of squamous cell carcinomas (SCC) is very limited. In this study we confirmed the existence of a tumor suppressor gene (TSG) on human chromosome 7 (hchr 7) that suppresses the tumorigenicity of squamous cell carcinomas (SCCs). We injected seven clones of CH72 cells (a murine SCC-derived cell line) bearing a hchr 7 (CH72/hchr 7) introduced by microcell fusion, two clones bearing human chromosome 12 (CH72/hchr 12) and parental CH72 cells into athymic Balb/c nude mice. The sizes of the tumors were determined twice a week until tumors reached 12 mm diameter. In situ hybridization for centromeric repetitive sequences of the transferred chromosomes were performed on the cell lines injected and the tumors arising after the injection. Southern blots and polymerase chain reaction (PCR) amplifications of near terminal sequences and (CA) microsatellite repeats were done to test the integrity of the introduced chromosomes. Five out of seven CH72/hchr 7 clones had a twofold and threefold longer latency periods than CH72 cells. The remaining CH72/hchr 7 clones (MF 6 and 13 no. 4) had latency periods similar to that of parental CH72; MF 6 had a deletion in the introduced chromosome 7 involving q31.3-q31.3, whereas the other hybrid (MF 13 no. 4) seemed to have an intact hchr 7. Tumor-derived cells from CH72/hchr 7 hybrids with a delayed latency had lost centromeric and telomeric sequences of Chr 7. In contrast, tumors derived from the MF 6 and MF 13 no. 4 as well as the CH72/hchr 12 clones retained the introduced human chromosome as shown by chromosome 7 or 12 centromeric and telomeric sequences. These results indicate that the tumorigenicity of CH72 murine SCC cells was suppressed by hchr 7 and that the CH72/hchr 7 regain the tumorigenic phenotype after loss of the introduced chromosome, suggesting the presence of a TSG on hchr 7.
Zenklusen
J C
JC
University of Texas M.D. Anderson Cancer Center Science Park, Research Division, Smithville 78957.
Oshimura
M
M
Barrett
J C
JC
Conti
C J
CJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D002459:Cell Fusion; D002881:Chromosomes, Human, Pair 12; D002897:Chromosomes, Human, Pair 7; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010641:Phenotype; D014407:Tumor Cells, Cultured