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  • 1
    In: Cancer Science, Wiley, Vol. 96, No. 7 ( 2005-07), p. 409-413
    Abstract: N ‐Methyl‐ N′ ‐nitro‐ N ‐nitrosoguanidine (MNNG)‐induced rat stomach carcinomas are considered to be a good model for differentiated‐type human stomach carcinomas. However, as for their molecular basis, only infrequent mutations of Catnb ( β ‐ catenin ) and Trp53 ( p53 ) have been observed. Here, we carried out a whole‐genome analysis of loss of heterozygosity (LOH) using 21 stomach carcinomas induced by MNNG in F 1 hybrids of ACI and BUF rats, and also analyzed promoter methylation of four tumor‐suppressor genes. LOH analysis was performed using 130 polymorphic markers covering rat chromosomes 1–20 with an average interval of 20 Mbp. Despite adapting conditions so that LOH could be detected with up to a 50% contamination of stromal cells, no LOH was detected at any loci. CpG islands in putative promoter regions of four tumor‐suppressor genes, Cdh1 ( E‐cadherin ), Cdkn2a ( p16 ), Mlh1 , and Rassf1a , were analyzed by methylation‐specific polymerase chain reaction (PCR). However, no methylation was detected. In contrast, the promoter region of Pgc ( pepsinogen C ), which lacks a CpG island, was methylated in all 21‐cancer samples. These results indicated that LOH spanning a chromosomal region larger than 30–40 Mbp or silencing of Cdh1 , Cdkn2a , Mlh1 , and Rassf1a , was not involved in MNNG‐induced rat stomach carcinomas. The search for other genes involved in these carcinomas needs to be continued. ( Cancer Sci 2005; 96: 409  – 413)
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2005
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2005
    In:  Genetics Vol. 171, No. 3 ( 2005-11-01), p. 1231-1238
    In: Genetics, Oxford University Press (OUP), Vol. 171, No. 3 ( 2005-11-01), p. 1231-1238
    Abstract: Differential expression of mRNA among animal strains is one of the mechanisms for their diversity. cDNA microarray analysis of the prostates of BUF/Nac (BUF) and ACI/N (ACI) rats, which show different susceptibility to prostate cancers, found 195 differentially expressed genes. To identify loci that control differential expression of 13 genes with diverse expression levels, their expression levels were measured by quantitative RT-PCR in 89 backcross rats, and expression quantitative trait locus (eQTL) analysis was performed. Nine genes [Aldh1a1, Aldr1, Bmp6, Cdkn1a (p21), Cntn6, Ghr, Jund, Nupr1, and RT1-M3] were controlled by cis-acting loci. Cdkn1a, a cell cycle regulator and a candidate for a prostate cancer susceptibility gene, was mapped to its own locus and had polymorphisms, including a 119-bp insertion in the 5′ upstream region in BUF rats. Four genes (Kclr, Pbsn, Psat1, and Ptn) were controlled by trans-acting loci. Pbsn, a prostate-specific gene on chromosome X, was controlled by a QTL on chromosome 8. Depending upon which gene that we selected from the genes widely used for normalization (Actb, Gapd, or Ppia), different QTL were mapped for Kclr, Psat1, and Ptn. Normalization using Actb most appropriately explained the expression levels in a congenic strain for chromosome 3. eQTL analysis with precise measurement of expression levels and appropriate normalization was shown to be effective for mapping loci that control gene expression in vivo.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2005
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 65, No. 7 ( 2005-04-01), p. 2610-2616
    Abstract: 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 & gt;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.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
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