ABSTRACT
RHOA protein, a member of small GTPases family, is implicated in cell morphogenesis, adhesion, and in cell cycle regulation. RHOA gene (3p21.31) exhibits cell transformation activity, and therefore gene is considered as a potential oncogene. The aim of this study was to investigate RHOA transcription and copy number changes in three epithelial tumors (breast, renal cell and epithelial ovarian carcinomas, 45 tumor/normal pairs altogether). EII, HhaI, AciI n Bsh1236I). Hypomethylation of the RHOA promoter region in tumor DNA was observed two times more frequently than increased methylation. Moreover, all (15) cancer cases with hypomethylation of the RHOA gene showed a 2-10 fold increased expression of RHOA. It was concluded that gene copy multiplication and demethylation of the RHOA promoter region can contribute to transcription activation of this gene in epithelial tumors.
Subject(s)
DNA Methylation , Neoplasms, Glandular and Epithelial/genetics , Promoter Regions, Genetic , Transcription, Genetic , rhoA GTP-Binding Protein/genetics , Breast Neoplasms/genetics , Carcinoma, Renal Cell/genetics , Female , Gene Amplification , Gene Dosage , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/genetics , Ovarian Neoplasms/genetics , RNA, Messenger/geneticsABSTRACT
Active immunization of white rats with cholecystokinin-4 covalently linked to the antigen carrier BSA evoked long-lasting changes in the rats' behavior, which were in the opposite direction to the anxiogenic effects of cholecystokinin-4 itself, showing that immunization had anxiolytic effects. Immunoenzyme analysis demonstrated the presence of antibodies to cholecystokinin-4 in the serum of immunized rats. These data are interesting from the point of view of correcting pathological anxiety and fear states by inverse immunoregulation.
Subject(s)
Anxiety/immunology , Behavior, Animal/physiology , Tetragastrin/immunology , Alcohol Drinking/immunology , Animals , Anxiety/physiopathology , Conditioning, Operant/drug effects , Depression/psychology , Exploratory Behavior/physiology , Fear/physiology , Immunoenzyme Techniques , Male , Motor Activity/physiology , Pain Measurement/drug effects , Peptide Fragments/immunology , Rats , Rats, Wistar , Swimming/psychologyABSTRACT
Active immunisation of albino rats by the BSA-conjugated CCK-4 induced formation of antibodies to the CCK-4 and some long-term changes of the rat behaviour. These changes were contrary to anxiogenic effect of the CCK-4 and demonstrated an anxiolytic effect of the immunisation. The data obtained suggest a possibility of an immunocorrection of pathological anxiety and fear by an inverse immunoregulation.
Subject(s)
Antibodies/pharmacology , Behavior, Animal/drug effects , Tetragastrin/immunology , Alcohol Drinking , Animals , Antibodies/blood , Antibodies/chemistry , Avoidance Learning/drug effects , Enzyme-Linked Immunosorbent Assay , Exploratory Behavior/drug effects , Maze Learning/drug effects , Motor Activity/drug effects , Pain Threshold , Rats , Rats, Wistar , Serum Albumin/chemistry , Tetragastrin/pharmacology , VaccinationABSTRACT
Parenteral administration of des-BOC-Pentagastrin induced the anxiety and fear manifestations, depressing also explorative behaviour in open field experiments in rats. Intranasal administration evoked similar effects, whereas pentagastrin reduced the anxiety level, increasing explorative behaviour. Pentagastrin and des-BOC-Pentagastrin displayed antagonism at the receptor level.