RESUMEN
<p><b>AIM</b>The 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).</p><p><b>METHODS</b>Gelatin 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.</p><p><b>RESULTS</b>Gelatin 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.</p><p><b>CONCLUSION</b>The 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.</p>
Asunto(s)
Animales , Humanos , Masculino , Ratones , Ratas , Animales Modificados Genéticamente , División Celular , Cromosomas Humanos Par 10 , Gelatina , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Metástasis de la Neoplasia , Genética , Neoplasias de la Próstata , Genética , Patología , Neoplasias Cutáneas , Genética , Patología , Células Tumorales CultivadasRESUMEN
<p><b>AIM</b>Chromosome 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.</p><p><b>METHODS</b>Human chromosome 13 was introduced into highly metastatic rat prostate cancer cells via microcell-mediated chromosome transfer.</p><p><b>RESULTS</b>Microcell 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.</p><p><b>CONCLUSION</b>Human 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.</p>