Abstract: |
Analysis of the cell-surface antigenic phenotypes of normal and malignant renal cells demonstrates that ≃90% of cultured normal human kidney cells and virtually all renal cell carcinomas (RCC) derive from the proximal tubule (PT) cell of the nephron. In the present study, the v-src oncogene was introduced into cultured normal human PT cells, and the effects of the v-src-encoded protein (pp60(v-src)) on the biologic and genetic phenotype of these cells were determined. V-src-containing PT cells underwent a series of phenotypic changes characteristic of renal cells in vivo. These included (i) alterations in morphology, (ii) an increase in proliferative capacity, (iii) loss of contact inhibition, (iv) immortalization and (v) tumorigenicity. Moreover, v-src-infected PT cells developed non-random clonal karyotypic abnormalities which are commonly observed in RCCs, including a deletion of chromosomal region 3p14-21, one of the most frequent deletions observed in human renal tumors. These results indicate that pp60(v-src) can initiate a complex process leading to the transformation of PT cells. This process includes the induction of genetic instability. Finally, these data provide experimental evidence corroborating cytogenetic and molecular data that a deletion of genes on chromosome 3p is a critical event in the transformation of the human renal cell. |
Keywords: |
human cell; gene deletion; mutation; animal; mice; cells, cultured; cell growth; morphology; kidney carcinoma; kidney neoplasms; cell transformation, neoplastic; immunoenzyme techniques; chromosome aberration; oncogene; carcinoma, renal cell; mice, nude; cell transformation; carcinogenicity; transplantation, heterologous; neoplasm transplantation; karyotyping; chromosome 3p; retrovirus; retroviridae; chromosomes, human, pair 3; contact inhibition; kidney proximal tubule; kidney tubules, proximal; chromosome banding; blotting, southern; oncogene protein pp60(v-src); precipitin tests; unidentified retrovirus; human; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; genes, src; kidney cell culture
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