RGD Reference Report - Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis. - Rat Genome Database

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Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis.

Authors: Hagan, S  Al-Mulla, F  Mallon, E  Oien, K  Ferrier, R  Gusterson, B  Garcia, JJ  Kolch, W 
Citation: Hagan S, etal., Clin Cancer Res. 2005 Oct 15;11(20):7392-7.
RGD ID: 2302868
Pubmed: PMID:16243812   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-05-0283   (Journal Full-text)

PURPOSE: Raf-1 kinase inhibitor protein (RKIP) was originally identified as the first physiologic inhibitor of the Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathway. This pathway regulates fundamental cellular functions, including those that are subverted in cancer cells, such as proliferation, transformation, survival, and metastasis. Recently, RKIP has been recognized as a strong candidate for a metastasis suppressor gene in cell and animal model systems. Therefore, we investigated whether RKIP expression is altered in clinical specimens of human primary breast cancers and their lymph node metastases. EXPERIMENTAL DESIGN: Paraffin-embedded tumor samples from 103 breast cancer patients were examined immunohistochemically for the expression of RKIP, activated ERK, and apoptosis. The specificity of the antibodies used was validated by competition experiments with purified recombinant RKIP protein. RESULTS: RKIP expression was high in breast duct epithelia and retained to varying degrees in primary breast tumors. However, in lymph node metastases, RKIP expression was highly significantly reduced or lost (P = 0.000003). No significant correlations were observed between RKIP expression and histologic type, tumor differentiation grade, size, or estrogen receptor status. CONCLUSION: This is the first study of RKIP expression in a large clinical cohort. It confirms the results of cell culture and animal studies, suggesting that in human breast cancer, RKIP is a metastasis suppressor gene whose expression must be down-regulated for metastases to develop. RKIP expression is independent of other markers for breast cancer progression and prognosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PEBP1HumanLymphatic Metastasis  IEP associated with Breast NeoplasmsRGD 
Pebp1RatLymphatic Metastasis  ISOPEBP1 (Homo sapiens)associated with Breast NeoplasmsRGD 
Pebp1MouseLymphatic Metastasis  ISOPEBP1 (Homo sapiens)associated with Breast NeoplasmsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pebp1  (phosphatidylethanolamine binding protein 1)

Genes (Mus musculus)
Pebp1  (phosphatidylethanolamine binding protein 1)

Genes (Homo sapiens)
PEBP1  (phosphatidylethanolamine binding protein 1)


Additional Information