Expression of integrin-linked kinase is increased in differentiated cells.
Integrin-linked kinase (ILK), a mediator of beta integrin signals, has emerged as a therapeutic target in malignant tumors. Because malignant transformation is accompanied by dedifferentiation, ILK expression was evaluated in diverse normal and tumor tissue samples with regard to tissue differentiation. In single sections and in a tissue microarray (323 tumor tissues, 181 normal tissues), immunohistochemistry was performed [ILK, Akt, phospho-Akt-S473, loricrin, transforming growth factor beta2 (TGFbeta2)], and staining intensities were semiquantitatively scored. Increased ILK expression was clearly associated with increased differentiation in normal gastrointestinal, neural, bone marrow, renal tissue, and in more differentiated areas of malignant tumors. ILK colocalized with its putative downstream target Akt and with loricrin or TGFbeta2. Our findings clearly show that elevated levels of ILK are associated with cellular differentiation in high turnover tissues but not generally with a malignant phenotype. Our study indicates that ILK is not a general molecular target for cancer therapy but rather an indicator of differentiation. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.
Haase
Michael
M
OncoRay-Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstrasse 74/PF 86, 01307 Dresden, Germany.
Gmach
Christine C
CC
Eke
Iris
I
Hehlgans
Stephanie
S
Baretton
Gustavo B
GB
Cordes
Nils
N
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D000099200:Scaffold Protein ILK
D015415:Biomarkers; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK