RGD Reference Report - Linkage and microarray analyses of susceptibility genes in ACI/Seg rats: a model for prostate cancers in the aged. - Rat Genome Database

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Linkage and microarray analyses of susceptibility genes in ACI/Seg rats: a model for prostate cancers in the aged.

Authors: Yamashita, S  Suzuki, S  Nomoto, T  Kondo, Y  Wakazono, K  Tsujino, Y  Sugimura, T  Shirai, T  Homma, Y  Ushijima, T 
Citation: Yamashita S, etal., Cancer Res 2005 Apr 1;65(7):2610-6.
RGD ID: 1358944
Pubmed: PMID:15805257   (View Abstract at PubMed)
DOI: DOI:10.1158/0008-5472.CAN-04-2932   (Journal Full-text)

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.

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Strains with Phenominer Data Strains with phenominer data
ACI/SegHsd F344/Jcl

Objects Annotated

Prcr1  (Prostate cancer resistance QTL 1)
Prcr2  (Prostate cancer resistance QTL 2)
Prcs1  (Prostate cancer susceptibility QTL 1)
Prcs2  (Prostate cancer susceptibility QTL 2)
Tescar1  (Testicular tumor resistance QTL 1)

ACI/SegHsd  (NA)
F344/Jcl  (NA)

Additional Information