The COOH-terminal Src kinase Csk is a tumor antigen in human carcinoma

The cytoplasmic tyrosine kinase cSrc is involved in the regulation of many important cellular functions including cell growth and transformation, and its activity is down regulated by phosphorylation of the Tyr530 residue by the COOH-terminal Src tyrosine kinase, Csk. Because cSrc was previously fou nd overexpressed, activated, and in some cases mutated in carcinoma, we inv estigated whether it could act as a tumor antigen. We show that whereas no autoantibodies were found against cSrc or its relative Fyn, up to 20% of pa tients with carcinoma had high-affinity autoantibodies against Csk. Immunit y mainly resulted from a secondary response, as indicated by the presence o f IsGI in the sera. Antibodies were linked to the cancer because they were not detected in healthy subjects nor in patients with unrelated diseases, a nd their levels decreased in the sera of patients after surgical resection. Furthermore, they behaved as early markers of epithelial transformation be cause they were present in sera of patients,vith early-stage tumors and pre cancerous lesions such as colorectal polyps and in sera of patients that we re scored negative for other cancer serological markers (CEA, CA15-3, CA19- 9, p53 antibodies). Finally the presence of these antibodies was attributed , at least in part, to a substantial elevation of Csk protein levels in the corresponding tumors. However a strong increase in Src activity was also o bserved in these tissues, which suggested that Csk cannot regulate Src-Like activity in carcinoma, Taken together, these data demonstrate that Csk act s as an autoantigen, and the detection of anti-Csk antibodies may have pote ntial diagnostic usefulness in the early detection and postoperative follow up of patients with carcinoma.