AIMChromosome 13 is one of the most frequently altered chromosomes in prostate cancer. The present study was undertaken to examine the role of human chromosome 13 in the progression of prostate cancer.

METHODSHuman chromosome 13 was introduced into highly metastatic rat prostate cancer cells via microcell-mediated chromosome transfer.

RESULTSMicrocell hybrid clones containing human chromosome 13 showed suppression of metastasis to the lung without any suppression of tumorigenicity, except for one clone, which contained the smallest sized human chromosome 13 and did not show any suppression on lung metastasis. Expression of two known tumor suppressor genes, BRCA2 and RB1, which map to chromosome 13, was examined by reverse transcription- polymerase chain reaction analysis. BRCA2 was expressed only in the metastasis-suppressed microcell-hybrid clones, whereas RB1 was expressed in all clones.

CONCLUSIONHuman chromosome 13 contains metastasis suppressor gene(s) for prostate cancer derived from rat. Furthermore, the RB1 gene is unlikely to be involved in the suppression of metastasis evident in this system.

Animals ; Animals, Genetically Modified ; Cell Division ; genetics ; Chromosome Aberrations ; Chromosome Mapping ; Chromosomes, Human, Pair 13 ; Disease Progression ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Kinetics ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms ; genetics ; pathology ; prevention & control ; Rats ; genetics

AIMThe metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones).

METHODSGelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed.

RESULTSGelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone.

CONCLUSIONThe human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.

Animals ; Animals, Genetically Modified ; Cell Division ; Chromosomes, Human, Pair 10 ; Gelatin ; analysis ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Metastasis ; genetics ; Prostatic Neoplasms ; genetics ; pathology ; Rats ; Skin Neoplasms ; genetics ; pathology ; secondary ; Tumor Cells, Cultured