The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.
- Klíčová slova
- auditory system, inferior colliculus, inhibition, sound processing, transcription factor ISL1,
- MeSH
- colliculus inferior metabolismus fyziologie MeSH
- exprese genu genetika MeSH
- lidé MeSH
- mozek fyziologie MeSH
- myši transgenní MeSH
- myši MeSH
- neurony fyziologie MeSH
- promotorové oblasti (genetika) genetika MeSH
- proteiny s homeodoménou LIM genetika metabolismus MeSH
- sluch MeSH
- sluchová percepce genetika fyziologie MeSH
- sluchové kmenové evokované potenciály fyziologie MeSH
- sluchový práh fyziologie MeSH
- transkripční faktor PAX2 genetika MeSH
- transkripční faktory genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- insulin gene enhancer binding protein Isl-1 MeSH Prohlížeč
- PAX2 protein, human MeSH Prohlížeč
- Pax2 protein, mouse MeSH Prohlížeč
- proteiny s homeodoménou LIM MeSH
- transkripční faktor PAX2 MeSH
- transkripční faktory MeSH
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
Pax transcription factors are evolutionarily conserved regulators of eye development and can be distinguished on the basis of three functional domains: two DNA-binding domains (the paired domain and the paired-type homeodomain), and the octapeptide motif. PaxB of the eyed cubozoan jellyfish, Tripedalia cystophora, is characterized by a Pax2-like paired domain and octapeptide, and a Pax6-like homeodomain. In mice, functionally distinct Pax6 and Pax2 proteins have unique as well as redundant roles in eye morphogenesis. Here, we show that expression of the jellyfish PaxB gene in mouse embryonic eye tissues impairs normal development of lens and retina. Our data show that PaxB misexpression leads to a downregulation of endogenous Pax6 protein in the prospective lens and in subsets of cells within the inner nuclear layer of transgenic retina. In addition to Pax6 downregulation, the expression of PaxB leads to an almost complete loss of amacrine cells in the adult transgenic retina, a phenotype that differs from a loss-of-function of the Pax6 gene. The present data suggest that PaxB, due to its Pax2-like paired domain and Pax-6 like homeodomain, disturbs the transcriptional network regulated by Pax6 in the developing lens and retina. Taken together, our data suggest that molecular properties of individual mouse Pax2 and Pax6 proteins are essential determinants of mouse eye development and cannot be substituted for by jellyfish PaxB which possesses elements of vertebrate Pax2 and Pax6.
- MeSH
- down regulace MeSH
- embryo savčí embryologie metabolismus MeSH
- fenotyp MeSH
- homeodoménové proteiny genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- oči embryologie metabolismus MeSH
- oční proteiny genetika metabolismus MeSH
- represorové proteiny genetika metabolismus MeSH
- Scyphozoa genetika metabolismus MeSH
- transkripční faktor PAX2 genetika metabolismus MeSH
- transkripční faktor PAX6 MeSH
- transkripční faktory Otx genetika metabolismus MeSH
- transkripční faktory paired box genetika metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- homeodoménové proteiny MeSH
- oční proteiny MeSH
- Pax6 protein, mouse MeSH Prohlížeč
- represorové proteiny MeSH
- transkripční faktor PAX2 MeSH
- transkripční faktor PAX6 MeSH
- transkripční faktory Otx MeSH
- transkripční faktory paired box MeSH
BACKGROUND: Sporadic renal cell carcinoma is one of the most common kidney malignancies in adults (85%). According to the IARC (The International Agency of Research on Cancer) Czech Republic has the first world position in the incidence and mortality for RCC. The prognosis of RCC is very poor because of high mortality around 70 to 50% and unpredictable progression after tumor removal. More precise molecular prognostic markers are required. Genes PAX2 and PAX8 control cell division during embryonic development and plays crucial role in tumor development because of stimulation of cell proliferation and/or inhibition of apoptotic program. METHODS AND RESULTS: Our RCC sample collection contains 64 tumor samples and 10 "normal" renal samples extracted from the affected kidney. mRNA was isolated from all samples and converted into cDNA. Expression of PAX genes was analyzed by using relative quantification real-time PCR with TaqMan labelled probe and GAPDH gene as an endogenous control. CONCLUSIONS: Expression of PAX2 gene was found in 97% and expression of PAX8 gene was found in 89% of analyzed tumor samples. The expression of both target genes was found in all "normal" renal samples. The level of expression of both PAX genes was very variable with the range from hundred times lower to forty times higher in comparison with the expression of chosen endogenous control. There were found no correlations between the expression of target genes and clinical-histological markers. These results do not have prognostic value yet because of short duration of patient observation. Follow-up clinical data are essential for completion of this research.
- MeSH
- exprese genu * MeSH
- karcinom z renálních buněk genetika MeSH
- ledviny metabolismus MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory ledvin genetika MeSH
- prognóza MeSH
- transkripční faktor PAX2 genetika MeSH
- transkripční faktor PAX8 MeSH
- transkripční faktory paired box genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové biomarkery MeSH
- PAX2 protein, human MeSH Prohlížeč
- PAX8 protein, human MeSH Prohlížeč
- transkripční faktor PAX2 MeSH
- transkripční faktor PAX8 MeSH
- transkripční faktory paired box MeSH
