Comparative study of expression of adaptor proteins Ruk/CIN85 and CD2AP/CMS in normal andtumor human uterus tissues

Abstract

Adaptor proteins play an important role in facilitating protein-protein interactions and subsequent formation of signalling networks. These proteins recruit binding partners to a specific location inside the cell, and also regulate their activity. Adaptor protein Ruk/CIN85 and its structural and functional homologue CD2AP/CMS are important components of different regulatory pathways involved in control of cell proliferation, adhesion, invasion and survival, and, thus, can play a role in uterine carcinogenesis. In this work, we set out a comparative study of expression of Ruk/CIN85 and CD2AP/CMS at the level of mRNA and protein in intact uterine tissues, as well as in benign and malignant uterine tumors of different histological types. In most cases, an increase of expression levels of Ruk/CIN85 full-length form mRNA and protein, as well as CD2AP/CMS protein, were observed in uterine tumors, comparing with surrounding normal uterine tissues. Characteristic feature of conditionally normal uterine tissues, as well as benign uterine lesions, was an elevated content of high-molecular mass Ruk/CIN85 forms of 140 and 130 kDa, while an increased expression level of low-molecular mass 40 and 30 kDa Ruk/CIN85 forms was observed in the malignant tissue samples. Our findings suggest that an abnormal expression patterns of adaptor proteins Ruk/CIN85 and CD2AP/CMS in uterine tumors, and, thus, the corresponding changes in the activity of downstream signalling pathways, might be involved in maintenance of the malignant phenotype.Key words: tumorigenesis, adaptor proteins, Ruk/CIN85, CD2AP/CMS, benign and malignant uterine tumors.Abbreviations: Ruk/CIN85, regulator of ubiquitous kinase/Cbl-interacting protein of 85 kDa; CD2AP/CMS, CD2 associated protein/Cas ligand with multiple SH3 domains; Biol. Stud. 2009: 3(3); 5-16 •

Scientific and practical activity of the Laboratory of Cell Signaling Mechanisms of the Palladin Institute of Biochemistry of NAS of Ukraine

“…Показано, що зразки нормальної тканини матки характеризу-ються підвищеним вмістом високомолекуляр-них форм цього протеїну (140 і 130 кДа), тоді як зразки пухлин матки -високим вмістом низько-молекулярних форм (40 і 30 кДа). Одержані дані щодо підвищення рівня експресії Ruk/CIN85 у пухлинах молочної залози та матки вказують на те, що ці адаптерні протеїни можуть слугувати тканиноспецифічними маркерами пухлинного процесу і його прогресії, бути прогностичними факторами і потенційними мішенями для роз-робки фармакологічних препаратів скерованої дії [2][3][4].…”