Basaraba O. Expression of adapter proteins of (Ruk/CIN85)/(CD2AP/CMS) family and mechanisms of their effects in human breast and uterine cancer

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0410U002366

Applicant for

Specialization

  • 03.00.04 - Біохімія

17-05-2010

Specialized Academic Board

Д 26.240.01

Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Essay

Investigation object: molecular mechanisms of carcinogenesis. The aim - study of adapter proteins Ruk/CIN85 and CD2AP/CMS expression peculiarities in human breast and uterine tumors and signalling mechanisms involved in the realization of their biological effects on models of tumor cell lines in vitro. Methods - biochemical and molecular-biological. The experimental data indicate the significant increase of Rukl/CIN85 and CD2AP/CMS expression in breast and uterine tumors Therefore, adapter proteins Rukl/CIN85 and CD2AP/CMS might be used as tissue-specific tumor markers, prognostic factors in cancer development and potential pharmacological targets for developing of anti-cancer drugs. Novelty - for the first time, increase of Rukl/CIN85 and CD2AP/CMS expression levels was revealed in samples of breast and uterine tumors in comparison with conventionally normal tissues; demonstrated that sublines of breast adenocarcinoma MCF-7 cells with stable overexpression of Rukl/CIN85 characterized increase of migration and changes in dynamics as well as intensity of Erk1/2- and Akt-dependent signalling induced by EGF. For the first time, androgen receptor was identified in human uterine adenocarcinoma HeLa cells; DHT-dependent complex formation between Rukl/CIN85 and androgen receptor as well as the role of Rukl/CIN85 in rapid non-genomic effects of androgen receptor were shown. Field of application: medical, scientific and educational institutions with medical and biological specialization.

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