title: PRKAR1A gene analysis and protein kinase A activity in endometrial tumors.
abstract: PRKAR1A codes for the type 1a regulatory subunit (RIα) of the cAMP-dependent protein kinase A (PKA), an enzyme with an important role in cell cycle regulation and proliferation. PKA dysregulation has been found in various tumors, and PRKAR1A-inactivating mutations have been reported in mostly endocrine neoplasias. In this study, we investigated PKA activity and the PRKAR1A gene in normal and tumor endometrium. Specimens were collected from 31 patients with endometrial cancer. We used as controls 41 samples of endometrium that were collected from surrounding normal tissues or from women undergoing gynecological operations for other reasons. In all samples, we sequenced the PRKAR1A-coding sequence and studied PKA subunit expression; we also determined PKA activity and cAMP binding. PRKAR1A mutations were not found. However, PKA regulatory subunit protein levels, both RIα and those of regulatory subunit type 2b (RIIβ), were lower in tumor samples; cAMP binding was also lower in tumors compared with normal endometrium (P<0.01). Free PKA activity was higher in tumor samples compared with that of control tissue (P<0.01). There are significant PKA enzymatic abnormalities in tumors of the endometrium compared with surrounding normal tissue; as these were not due to PRKAR1A mutations, other mechanisms affecting PKA function ought to be explored.
authors.affiliation: First Department of Obstetrics and Gynecology, Athens University Medical School, Alexandra Hospital, 115 28 Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Tsigginou
authors.forename: E
authors.initials: E
authors.lastname: Bimpaki
authors.forename: M
authors.initials: M
authors.lastname: Nesterova
authors.forename: A
authors.initials: A
authors.lastname: Horvath
authors.forename: S
authors.initials: S
authors.lastname: Boikos
authors.forename: C
authors.initials: C
authors.lastname: Lyssikatos
authors.forename: C
authors.initials: C
authors.lastname: Papageorgiou
authors.forename: C
authors.initials: C
authors.lastname: Dimitrakakis
authors.forename: A
authors.initials: A
authors.lastname: Rodolakis
authors.forename: C A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: A
authors.initials: A
authors.lastname: Antsaklis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D017868:Cyclic AMP-Dependent Protein Kinases