Cooperative effects of INK4a and ras in melanoma susceptibility in vivo Journal Article
| Authors: | Chin, L.; Pomerantz, J.; Polsky, D.; Jacobson, M.; Cohen, C.; Cordon-Cardo, C.; Horner Ii, J. W.; DePinho, R. A. |
| Article Title: | Cooperative effects of INK4a and ras in melanoma susceptibility in vivo |
| Abstract: | The familial melanoma gene (INK4a/MTS1/CDKN2) encodes potent tumor suppressor activity. Although mice null for the ink4a homolog develop a cancer-prone condition, a pathogenetic link to melanoma susceptibility has yet to be established. Here we report that mice with melanocyte-specific expression of activated H-ras(G12V) on an ink4a-deficient background develop spontaneous cutaneous melanomas after a short latency and with high penetrance. Consistent loss of the wild-type ink4a allele was observed in tumors arising in ink4a heterozygous transgenic mice. No homozygous deletion of the neighboring ink4b gene was detected. Moreover, as in human melanomas, the p53 gene remained in a wild-type configuration with no observed mutation or allelic loss. These results show that loss of ink4a and activation of Ras can cooperate to accelerate the development of melanoma and provide the first in vivo experimental evidence for a causal relationship between ink4a deficiency and the pathogenesis of melanoma. In addition, this mouse model affords a system in which to identify and analyze pathways involved in tumor progression against the backdrop of genetic alterations encountered in human melanomas. |
| Keywords: | controlled study; gene mutation; exons; nonhuman; polymerase chain reaction; mouse; animals; mice; mice, knockout; allele; animal tissue; cancer susceptibility; melanoma; skin neoplasms; melanocyte; animal experiment; animal model; chromosome 9p; gene product; oncogene h ras; mice, transgenic; cancer inhibition; tumor suppressor gene; ras protein; cyclin-dependent kinase inhibitor p16; dna primers; genes, ras; transgenic; ras; p53; genes, p16; disease susceptibility; ink4a; eye neoplasms; humans; priority journal; article; ink4b |
| Journal Title: | Genes and Development |
| Volume: | 11 |
| Issue: | 21 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 1997-11-01 |
| Start Page: | 2822 |
| End Page: | 2834 |
| Language: | English |
| PUBMED: | 9353252 |
| PROVIDER: | scopus |
| PMCID: | PMC316663 |
| DOI: | 10.1101/gad.11.21.2822 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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