Human chromosome 16 suppresses metastasis but not tumorigenesis in rat prostatic tumor cells.
Genomic aberrations at the chromosome 16q arm are one of the most consistent abnormalities observed by loss of heterozygosity and comparative 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 introduce human chromosome 16 into the highly metastatic Dunning rat prostatic cancer cell line, AT6.1. The metastatic ability of the resultant microcell hybrid clones was then tested in a standard spontaneous metastasis assay using SCID mice. When the microcell-mediated chromosome transfer hybrid cells containing whole human chromosome 16 were injected, the number of metastatic lesions in the lung was significantly reduced as much as 99% on average. Therefore, chromosome 16 has a strong activity to suppress the metastatic ability of AT6.1 cells while it did not affect the tumorigenesis and tumor growth rate. A PCR analysis of various microcell hybrid clones with sequence-tagged site markers indicates that the metastasis suppressor activity is located in the q24.2 region of chromosome 16. Our results are consistent with the previous 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.
Mashimo
T
T
Department of Medical Microbiology and Immunology, Southern Illinois University, School of Medicine, Springfield 62702, USA.
Watabe
M
M
Cuthbert
A P
AP
Newbold
R F
RF
Rinker-Schaeffer
C W
CW
Helfer
E
E
Watabe
K
K
D000818:Animals; D015820:Cadherins / Q000235:genetics; D002885:Chromosomes, Human, Pair 16; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D015820:Cadherins