T. Mashimo et al., HUMAN-CHROMOSOME-16 SUPPRESSES METASTASIS BUT NOT TUMORIGENESIS IN RAT PROSTATIC TUMOR-CELLS, Cancer research, 58(20), 1998, pp. 4572-4576
Genomic aberrations at the chromosome 16q arm are one of the most cons
istent abnormalities observed by loss of heterozygosity and comparativ
e genomic hybridization analyses in human prostate cancer, suggesting
that there are tumor suppressor or metastasis suppressor genes encoded
by this chromosomal region, To functionally identify such suppressor
genes, we have conducted microcell-mediated chromosome transfer to int
roduce human chromosome 16 into the highly metastatic Dunning rat pros
tatic cancer cell line, AT6.1. The metastatic ability of the resultant
microcell hybrid clones was then tested in a standard spontaneous met
astasis assay using SCID mice. When the microcell-mediated chromosome
transfer hybrid cells containing whole human chromosome 16 were inject
ed, the number of metastatic lesions in the lung was significantly red
uced as much as 99% on average. Therefore, chromosome 16 has a strong
activity to suppress the metastatic ability of AT6.1 cells while it di
d not affect the tumorigenesis and tumor growth rate. A PCR analysis o
f various microcell hybrid clones with sequence-tagged site markers in
dicates that the metastasis suppressor activity is located in the q24.
2 region of chromosome 16, Our results are consistent with the previou
s finding that the region of human chromosome 16q has frequent loss of
heterozygosity in prostate cancer patients and suggest that there is
a metastasis suppressor gene in this region that may play an important
role in the progression of prostate cancer.