Carcinogenesis, Vol 18, 1751-1755, Copyright © 1997 by Oxford University Press
TR Devereux, CH Anna, AC Patel, CM White, MF Festing and M You
In this study we investigated the mouse mad-related genes, Smad4/Dpc4 and
Smad2 (homolog of JV18-1), as candidates for involvement in lung tumor
resistance and suppression. These genes are located in a region of mouse
chromosome 18 that is syntenic with human 18q21.1, where several genes that
are mutated in various cancers have been mapped. A newly identified murine
lung tumor resistance locus, Par2 has also been mapped to this region of
chromosome 18. We found no mutations in the coding regions of either gene
in 11 lung tumors from B6CF1 (C57BL/6 x BALB/c) mice by RT-PCR and
SSCP/RFLP, suggesting that these genes are not mutated in lung
carcinogenesis in this strain. Moreover, loss of heterozygosity in this
region of chromosome 18 was not detected in 28 lung adenocarcinomas from
B6CF1 mice, 17 lung adenocarcinomas from B6C3F1 mice or 18 lung
adenocarcinomas from AB6F1 mice. These data provide evidence that a
'classical' tumor suppressor gene for mouse lung carcinogenesis in these
strains does not reside in this region. In order to investigate Smad4/Dpc4
and Smad2 as candidates for the Par2 resistance locus mapped to this
region, we also sequenced the coding regions of both genes in cDNA from
normal lungs of A/J, BALB/c and C57BL/6 inbred strains of mice. No
polymorphisms were detected in the coding region of Smad4. In Smad2, two
sequence polymorphisms were identified that are not in the conserved
regions of the gene. Northern blot analysis revealed no differential
expression in normal lung tissue among the three strains for either gene.
Thus, in this study we found no evidence that either Smad4 or Smad2
represents the Par2 lung tumor resistance locus or is a lung tumor
suppressor gene in the B6CF1 mice.
ARTICLES
Smad4 (homolog of human DPC4) and Smad2 (homolog of human JV18-1): candidates for murine lung tumor resistance and suppressor genes
Laboratory of Molecular Carcinogenesis, NIEHS, Research Triangle Park, NC 27709, USA.
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