1058 POSTER Adaptor Protein Ruk/CIN85 Expression in Human Tumours

Abstract

Background: The characterization of molecular alterations in each single tumour is at the basis of personalized anticancer approaches aimed to give each patient the most appropriate therapy. Adaptor/scaffold proteins are the key components of signalling networks involved in the control of cell physiology. In particular, by binding to numerous effector proteins adaptor/scaffold protein Ruk/CIN85 assembles multimeric complexes implicated in control of receptor tyrosine kinase signalling, neuronal and T cells apoptosis, adhesion and invasion. Material and Methods: Using Western-blot analysis, samples of uterine cervix, stomach, skin, thyroid, brain tumours and adjacent normal tissues were analyzed. Results: Increase of Ruk/CIN85 full-length form (p85) expression was revealed in uterine cervix, stomach and skin cancer samples in comparison with corresponding control samples. Down-regulation of p85 was revealed in the majority of thyroid tumour samples in comparison with adjacent normal tissue samples. Using anti-RukS Western-blot analysis, multiple molecular forms of CIN85/Ruk with molecular weight of 140, 130, 85, 70, 56, 50, 40 and 38 kDa were detected. Changes in expression level of some Ruk/CIN85 multiple molecular forms as well as up-regulation of low-molecular mass forms (40 and 34 kDa) were detected in skin cancer samples. Expression level up-regulation of high-molecular (140 and 130 kDa) and low-molecular (40 and 34 kDa) Ruk/CIN85 multiple molecular forms of thyroid tumour, renal tumour and glioblastoma samples in comparison with conditionally normal tissue were revealed. The additional feature of Ruk/CIN85 forms expression patterns in uterine as well as stomach malignancies was the high content of p70, p40 and p34 forms while control tissue samples were characterized by the predominant increase of high molecular forms (p140, p130, p100). Conclusions: The obtained results suggest that changes in the expression level of multiple molecular forms of CIN85/Ruk in tumour samples can lead to the loss of coordinated control of apoptosis and proliferation in the transformed cells. These data will offer new opportunities for the identification and validation of key molecular tumour targets to be exploited for novel therapeutic approaches.