Specific induction of pp125 focal adhesion kinase in human breast cancer.
The pp125 focal adhesion kinase (FAK) is involved in integrin-mediated cell signalling and overexpressed in a variety of solid tumours. Focal adhesion kinase expression has been correlated to invasion and metastasis, but the data on breast cancer are inconclusive. We analysed FAK mRNA, protein levels and expression patterns in primary breast cancer and normal breast tissue. FAK expression on the functional protein level and mRNA was determined in 55 matched pairs of breast cancer and corresponding normal tissue by Western blot, immunohistochemistry and RT-PCR. Using a score ranging from 0 to +5 for Western blots, we determined in normal breast tissue a score of 1.51+/-0.84 (mean+/-standard deviation), which was strongly induced to 2.91 (+/-1.22) in breast cancers (P<0.001). Overall, 45 out of 55 tissue pairs (81.8%) showed this upregulation of FAK protein in tumours in comparison to normal tissue. Immunohistochemistry confirmed these findings with a significant higher score for tumours vs physiological tissue (1.0+/-0.63 vs 2.27+/-0.91; P=0.001). Interestingly, no overall significant difference in the mRNA levels (P=0.359) was observed. In conclusion, expression levels of the FAK protein are specifically upregulated in breast cancer in comparison to matched normal breast tissue supporting its pivotal role in neoplastic signal transduction and representing a potential marker for malignant transformation.
Watermann
D O
DO
Department of Obstetrics and Gynecology, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany.
Gabriel
B
B
Jäger
M
M
Orlowska-Volk
M
M
Hasenburg
A
A
zur Hausen
A
A
Gitsch
G
G
Stickeler
E
E
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D004789:Enzyme Activation; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human