The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.

• MeSH
• alfa receptor estrogenů genetika   metabolismus   MeSH
• antigen Ki-67 genetika   metabolismus   MeSH
• dospělí MeSH
• erbB receptory genetika   metabolismus   MeSH
• karcinom diagnóza   metabolismus   MeSH
• koaktivátor 3 jaderných receptorů genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mozku diagnóza   metabolismus   sekundární   MeSH
• nádory prsu diagnóza   metabolismus   MeSH
• receptor erbB-2 genetika   metabolismus   MeSH
• receptory progesteronu genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkripční faktor PAX2 genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa receptor estrogenů MeSH
• antigen Ki-67 MeSH
• erbB receptory MeSH
• ERBB2 protein, human MeSH Prohlížeč
• koaktivátor 3 jaderných receptorů MeSH
• NCOA3 protein, human MeSH Prohlížeč
• PAX2 protein, human MeSH Prohlížeč
• receptor erbB-2 MeSH
• receptory progesteronu MeSH
• transkripční faktor PAX2 MeSH

PURPOSE: Carriers of BRCA1/2 mutations are at high lifetime risk of breast cancer (BC); however, the BC onset broadly vary in individual patients. Recently, polyglutamine (poly-Q) repeat length polymorphism of the amplified in breast cancer 1 (AIB1) gene was analyzed as a risk factor influencing BC onset in BRCA1/2 mutation carriers with contradictory results. METHODS: We genotyped AIB1 poly-Q repeat in 243 BRCA1/2 mutation carriers, 61 patients with familial BC (negatively tested for the presence of BRCA1/2 mutation), 221 patients with sporadic BC, and 176 non-cancer controls using denaturing high-performance liquid chromatography and statistically evaluated the effect of AIB1 poly-Q repeat length polymorphism on BC onset. RESULTS: Having used previously published statistical analyses of AIB1 poly-Q repeat length (≥28 and ≥29 repeat cutpoints or analysis of AIB1 poly-Q repeat length as continuous variable), we did not find any association between AIB1 poly-Q repeat length and BC development in analyzed BC groups. However, the analysis of individual genotypes revealed that AIB1 genotype consisting of 28/28 glutamine repeats served as a protective factor in BRCA1 mutation carriers (HR = 0.64; 95% CI 0.41-0.99; P = 0.045) and as a risk factor in carriers of mutation in exon 11 of the BRCA2 gene (HR = 3.50; 95% CI 1.25-9.78; P = 0.017). CONCLUSIONS: Our results confirm that AIB1 poly-Q repeat length polymorphism does not influence the BC risk in general but suggest that the specific AIB1 genotypes should be considered in patients with BC carrying mutation in the BRCA1/2 genes.

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• geny BRCA1 MeSH
• geny BRCA2 MeSH
• heterozygot MeSH
• hodnocení rizik MeSH
• koaktivátor 3 jaderných receptorů genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádory prsu genetika   mortalita   MeSH
• peptidy genetika   MeSH
• polymorfismus genetický * MeSH
• proporcionální rizikové modely MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• koaktivátor 3 jaderných receptorů MeSH
• NCOA3 protein, human MeSH Prohlížeč
• peptidy MeSH
• polyglutamine MeSH Prohlížeč

BACKGROUND: The p160 steroid receptor coactivator (SRC) family is critical to the transcriptional activation function of nuclear hormone receptors. A key member of this family is SRC-3, initially found to be amplified and expressed in breast cancer it has subsequent been shown to be expressed in malignant disease arising from a wide range of other organs. An understanding of the potential role of SRC-3 in the pathogenesis and its possible prognostic role in a broad range of tumours will improve our general understanding of carcinogenesis as well as potentially leading to a new prognostic marker as well as new therapeutic targets. METHODS: Relevant papers were identified by searching the PubMed and MEDLINE databases for article published until 28th February 2009. Only articles published in English were considered. The search terms included "SRC-3", "AIB1" in association with the following terms: "human", "cancer" and "malignant disease". The search focused on malignant disease arising outside of the mammary gland. Full articles were obtained and references were checked for additional material when appropriate. RESULTS: SRC-3 is amplified and expressed in a wide spectrum of human malignant diseases and appears to be a potential prognostic marker in a number of different tumours. CONCLUSION: SRC-3 appears to be implicated in the possible risk of developing prostate and ovarian cancer. Its presence appears to be a marker of aggressive disease. Further research is required to determine its predictive and prognostic utility given the relative paucity of studies for each specific malignant disease.

• MeSH
• DNA rostlinná genetika   MeSH
• genetická predispozice k nemoci MeSH
• genetická transkripce genetika   MeSH
• koaktivátor 3 jaderných receptorů genetika   metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory genetika   metabolismus   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• DNA rostlinná MeSH
• koaktivátor 3 jaderných receptorů MeSH
• nádorové biomarkery MeSH
• NCOA3 protein, human MeSH Prohlížeč

Members of the nuclear receptor superfamily are ligand-regulated transcription factors involved in the control of a broad range of normal physiological and disease processes. The estrogen receptor alpha (ERalpha) is a member of the steriod receptor family, which is part of the nuclear receptor superfamily. ERalpha it is important for many biological processes and plays a key role in the pathogenesis of breast cancer. Gene regulation by ERalpha requires the recruitment of a multitude of transcriptional co-regulators to the promoters of estrogen-responsive genes. There is evidence in support of the involvement of these co-regulators in breast cancer progression. We review the role of steroid receptor co-activator-3 (SRC-3), which is frequently amplified in breast cancer, and its role in breast cancer risk, outcome and response to endocrine therapy in patients with breast cancer.

• MeSH
• alfa receptor estrogenů metabolismus   MeSH
• koaktivátor 3 jaderných receptorů metabolismus   MeSH
• lidé MeSH
• nádory prsu genetika   MeSH
• regulace genové exprese u nádorů * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alfa receptor estrogenů MeSH
• koaktivátor 3 jaderných receptorů MeSH
• NCOA3 protein, human MeSH Prohlížeč

Denaturing high-performance liquid chromatography (DHPLC) has been used for rapid and accurate DNA mutation analysis; to extend the DNA fragment lengths analysis. Recently, polymorphism in polyglutamine-coding region of Amplified In Breast cancer gene 1 (AIB1) was analyzed as an independent genetic risk factor influencing breast cancer onset in carriers of mutation in breast cancer predisposing gene 1 (BRCA1). We have implemented efficient, cost-effective and rapid method for analysis of the AIB1 polyglutamine repeat polymorphism based on DHPLC analysis (WAVE system) of unlabeled PCR products. This strategy can be useful for genotyping of other trinucleotide repeat polymorphisms using DHPLC in medium/high throughput settings.

• MeSH
• denaturace nukleových kyselin MeSH
• DNA nádorová chemie   genetika   MeSH
• DNA primery genetika   MeSH
• histonacetyltransferasy genetika   MeSH
• koaktivátor 3 jaderných receptorů MeSH
• lidé MeSH
• nádory prsu genetika   MeSH
• polymorfismus genetický * MeSH
• sekvence nukleotidů MeSH
• trans-aktivátory genetika   MeSH
• trinukleotidové repetice * MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA nádorová MeSH
• DNA primery MeSH
• histonacetyltransferasy MeSH
• koaktivátor 3 jaderných receptorů MeSH
• NCOA3 protein, human MeSH Prohlížeč
• trans-aktivátory MeSH