Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer.
BACKGROUND
The FAK gene encodes a 125-kDa tyrosine kinase (p125FAK) involved in signal transduction pathways used in cell adhesion, motility, and anchorage-independent growth. Because thyroid carcinomas have a wide variability in their propensity for invasion and metastasis, we studied the expression of FAK in a variety of thyroid tissues.


METHODS
We synthesized a recombinant N-terminal fragment of the human FAK protein and developed a specific polyclonal antisera. Using Western blot analysis, we assessed the levels of p125FAK expression in 30 human thyroid tissue samples from 27 patients that included paired normal and malignant specimens. Levels of FAK protein in individual tumors were quantitated by densitometric scanning of the immunoblots, and the results were correlated with tumor histology and biologic behavior.


RESULTS
The levels of FAK expression were directly correlated with thyroid carcinomas demonstrating the most aggressive phenotypes. The highest levels of p125FAK were seen in follicular carcinomas and tumors associated with distant metastatic foci. In contrast, neoplastic thyroid tissues with limited invasive potential, such as papillary carcinomas, follicular adenomas, and other nonmalignant thyroid lesions, showed minimal p125FAX expression.


CONCLUSIONS
Overexpression of FAK may be part of a mechanism for invasion and metastasis of thyroid cancer. Furthermore, the levels of p125FAK may serve as a marker of biologic behavior in this disease.
Owens
L V
LV
Department of Surgery, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Xu
L
L
Dent
G A
GA
Yang
X
X
Sturge
G C
GC
Craven
R J
RJ
Cance
W G
WG
D018263:Adenocarcinoma, Follicular / Q000201:enzymology / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013961:Thyroid Gland / Q000201:enzymology; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human