1. Cancer Res. 2005 Apr 1;65(7):2610-6.
Linkage and microarray analyses of susceptibility genes in ACI/Seg rats: a model
for prostate cancers in the aged.
Yamashita S(1), Suzuki S, Nomoto T, Kondo Y, Wakazono K, Tsujino Y, Sugimura T,
Shirai T, Homma Y, Ushijima T.
Author information:
(1)Carcinogenesis Division, National Cancer Center Research Institute, 1-1
Tsukiji 5-chome, Chuo-ku, Tokyo, Japan.
ACI/Seg (ACI) rats develop prostate cancers spontaneously with aging, similar to
humans. Here, to identify genes involved in prostate cancer susceptibility, we
did linkage analysis and oligonucleotide microarray analysis. Linkage analysis
was done using 118 effective rats, and prostate cancer susceptibility 1 (Pcs1),
whose ACI allele dominantly induced prostate cancers, was mapped on chromosome 19
[logarithm of odds (LOD) score of 5.0]. PC resistance 1 (Pcr1), whose ACI allele
dominantly and paradoxically suppressed the size of prostate cancers, was mapped
on chromosome 2 (LOD score of 5.0). When linkage analysis was done in 51 rats
with single or no macroscopic testicular tumors, which had larger prostates and
higher testosterone levels than those with bilateral testicular tumors, Pcs2 and
Pcr2 were mapped on chromosomes 20 and 1, respectively. By oligonucleotide
microarray analysis with 8,800 probe sets and confirmation by quantitative
reverse transcription-PCR, only two genes within these four loci were found to be
differentially expressed >1.8-fold. Membrane metalloendopeptidase (Mme), known to
inhibit androgen-independent growth of prostate cancers, on Pcr1 was expressed
2.0- to 5.5-fold higher in the ACI prostate, in accordance with its paradoxical
effect. Cdkn1a on Pcs2 was expressed 1.5- to 4.5-fold lower in the ACI prostate.
Additionally, genes responsible for testicular tumors and unilateral renal
agenesis were mapped on chromosomes 11 and 14, respectively. These results showed
that prostate cancer susceptibility of ACI rats involves at least four loci, and
suggested Mme and Cdkn1a as candidates for Pcr1 and Pcs2.
PMID: 15805257 [PubMed - indexed for MEDLINE]
PUBMED: 15805257
Find other GeneSets from this publication
GeneWeaver