RGD Reference Report - Changes in the renin angiotensin system during the development of colorectal cancer liver metastases. - Rat Genome Database

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Changes in the renin angiotensin system during the development of colorectal cancer liver metastases.

Authors: Neo, Jaclyn H  Ager, Eleanor I  Angus, Peter W  Zhu, Jin  Herath, Chandana B  Christophi, Christopher 
Citation: Neo JH, etal., BMC Cancer. 2010 Apr 10;10:134. doi: 10.1186/1471-2407-10-134.
RGD ID: 25671446
Pubmed: PMID:20380732   (View Abstract at PubMed)
PMCID: PMC2860361   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2407-10-134   (Journal Full-text)


BACKGROUND: Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease.
METHODS: Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software.
RESULTS: Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen.
CONCLUSIONS: These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Liver Metastasis  ISOAce (Mus musculus)25671446; 25671446associated with colorectal cancer and mRNA:increased expression:liver (mouse) RGD 
Liver Metastasis  IEP 25671446associated with colorectal cancer and mRNA:increased expression:liver (mouse) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ace  (angiotensin I converting enzyme)

Genes (Mus musculus)
Ace  (angiotensin I converting enzyme)

Genes (Homo sapiens)
ACE  (angiotensin I converting enzyme)


Additional Information