RGD Reference Report - A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model. - Rat Genome Database

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A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model.

Authors: Majeed, N  Blouin, MJ  Kaplan-Lefko, PJ  Barry-Shaw, J  Greenberg, NM  Gaudreau, P  Bismar, TA  Pollak, M 
Citation: Majeed N, etal., Oncogene. 2005 Jul 7;24(29):4736-40.
RGD ID: 2301422
Pubmed: PMID:15870705   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1208572   (Journal Full-text)

Circulating insulin-like growth factor-I (IGF-I) levels have been shown to be related to risk of prostate cancer in epidemiologic studies. While specific genetic loci responsible for interindividual variation in circulating IGF-I levels in normal men have not been identified, candidate genes include those involved in the growth hormone (GH)-IGF-I axis such as the hypothalamic factors GH releasing hormone (GHRH) and somatostatin and their receptors. To investigate the role of the GH-IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we generated mice genetically predisposed to prostate cancer (the TRAMP model) to be homozygous for lit, a mutation that inactivates the GHRH receptor (GHRH-R) and reduces circulating levels of GH and IGF-I. The lit mutation significantly reduced the percentage of the prostate gland showing neoplastic changes at 35 weeks of age (P=0.0005) and was also associated with improved survival (P<0.01). These data provide an example of a germ line mutation that reduces risk in an experimental prostate carcinogenesis model. The results suggest that prostate carcinogenesis and progression may be influenced by germ line variation of genes encoding signalling molecules in the GH-IGF-I axis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GHRHRHumanProstatic Neoplasms disease_progressionISOGhrhr (Mus musculus)DNA:transition:cds:p.D60G (mouse)RGD 
GhrhrRatProstatic Neoplasms disease_progressionISOGhrhr (Mus musculus)DNA:transition:cds:p.D60G (mouse)RGD 
GhrhrMouseProstatic Neoplasms disease_progressionIAGP DNA:transition:cds:p.D60G (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ghrhr  (growth hormone releasing hormone receptor)

Genes (Mus musculus)
Ghrhr  (growth hormone releasing hormone receptor)

Genes (Homo sapiens)
GHRHR  (growth hormone releasing hormone receptor)

Objects referenced in this article
Gene GHRH growth hormone releasing hormone Homo sapiens
Gene Ghrh growth hormone releasing hormone Mus musculus
Gene Ghrh growth hormone releasing hormone Rattus norvegicus

Additional Information