RGD Reference Report - Requirement for focal adhesion kinase in the early phase of mammary adenocarcinoma lung metastasis formation. - Rat Genome Database

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Requirement for focal adhesion kinase in the early phase of mammary adenocarcinoma lung metastasis formation.

Authors: Van Nimwegen, MJ  Verkoeijen, S  Van Buren, L  Burg, D  Van de Water, B 
Citation: van Nimwegen MJ, etal., Cancer Res. 2005 Jun 1;65(11):4698-706.
RGD ID: 2292560
Pubmed: PMID:15930288   (View Abstract at PubMed)
DOI: DOI:10.1158/0008-5472.CAN-04-4126   (Journal Full-text)

An increased expression of focal adhesion kinase (FAK) in a variety of cancers is associated with a poor disease prognosis. To study the role of FAK in breast tumor growth and metastasis formation, we used conditional doxycycline-regulated expression of a dominant-negative acting splice variant of FAK, FAK-related non-kinase (FRNK), in MTLn3 mammary adenocarcinoma cells in a syngeneic Fischer 344 rat tumor and metastasis model. In cell culture, doxycycline-mediated expression of FRNK inhibited MTLn3 cell spreading and migration in association with reduced formation of focal adhesions and phosphorylation of FAK on Tyr(397), but FRNK did not cause apoptosis. Continuous expression of FRNK decreased the primary tumor growth in the mammary fat pad by 60%, which was not due to induction of apoptosis. Lung metastasis formation was almost completely prevented when FRNK was already expressed 1 day before tumor cell injection, whereas expression of FRNK 11 days after injection did not affect lung metastasis formation. FRNK expression during the first 5 days was sufficient to block metastasis formation, excluding the possibility of FRNK-induced dormancy of tumor cells. Together, these data fit with a model wherein FAK is required for breast tumor cell invasion/migration processes that take place in the early phase of metastasis formation. Our findings suggest that FAK is a good candidate for therapeutic intervention of metastasis formation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Mammary Neoplasms  ISOPtk2 (Rattus norvegicus)2292560; 2292560 RGD 
Experimental Mammary Neoplasms  IMP 2292560 RGD 
Neoplasm Metastasis  ISOPtk2 (Rattus norvegicus)2292560; 2292560associated with Mammary Neoplasms and ExperimentalRGD 
Neoplasm Metastasis  IMP 2292560associated with Mammary Neoplasms and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptk2  (protein tyrosine kinase 2)

Genes (Mus musculus)
Ptk2  (PTK2 protein tyrosine kinase 2)

Genes (Homo sapiens)
PTK2  (protein tyrosine kinase 2)


Additional Information