Kallikrein-related peptidases 7 and 11 (KLK7/KLK11) share a high degree of structural similarity with PSA (KLK3) and other KLKs. The aim of this study was to evaluate differences in KLK7/ KLK11 expression in paired cancer/benign prostate foci and to determine possible associations with clinicopathological parameters. Seventy archived paraffin-embedded tissue samples obtained from radical prostatectomy were stained for KLK7, KLK11, PSA and PSMA and expression was evaluated semiquantitatively. The results showed statistically significant differences for all studied proteins between BPH and CaP foci. Both KLK7 (P=0.026) and KLK11 (P<0.001) expressions were decreased in prostate cancer cells compared to normal/benign prostate cells. Positive correlations were found for both KLK7 (Rs=0.74, P<0.001) and KLK11 (Rs=0.35, P=0.003) between CaP and BPH. We found a statistically significant upregulation of KLK11 in advanced cases compared to localized ones (P=0.026). For the first time, we report lower expression of KLK11 in CaP compared to BPH and slight upregulation of KLK11 in advanced tumors compared to localized ones. Our observations support the diagnostic potential of KLK7/KLK11 for early prostate cancers but further studies on larger cohorts are needed in order to validate the clinical value of these biomarkers and clarify their biological role in prostate development and tumorigenesis.
- MeSH
- hyperplazie prostaty enzymologie patologie MeSH
- imunohistochemie MeSH
- kalikreiny biosyntéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory prostaty enzymologie patologie MeSH
- senioři MeSH
- serinové endopeptidasy biosyntéza MeSH
- staging nádorů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Signaling through the androgen receptor (AR) plays a critical role in prostate cancer progression. The AR is a classical nuclear receptor (NR) providing a link between signaling molecule and transcription response. Histone deacetylase inhibitors- (HDACI) have antiproliferative and proapoptotic effects on prostate cancer cells and their implication in silence AR signaling may have potential therapeutic use. We aimed to study the inhibitory effects of the corepressor SMRT (Silencing Mediator for Retinoid and Thyroid -hormone receptors) which forms a complex together with nuclear receptor corepressor (N-CoR) and with histone deacetylase 3 (HDAC3) on AR activity.The androgen-sensitive prostate cancer cell line LNCaP and androgen-insensitive prostate cancer cell line C4-2 both AR-positive, and androgen-insensitive DU145 and PC3 prostate cancer cell lines were treated with two HDACIs, sodium butyrate (NaB) and/or trichostatin A (TSA). We amplified immunoprecipitated DNA by conventional PCR and in the -following step we used the chromatin immunoprecipitation (ChIP) analysis coupled with quantitative PCR for monitoring NaB induced formation of AR-SMRT/N-CoR complex binding on the PSA promoter. The co-immunoprecipitation assay revealed increase in AR-SMRT formation in NaB treated cells. Simultaneously, the Western blot analysis showed a significant decrease in AR protein expression. In conclusion, the inhibitory effect of NaB on AR gene expression seems to be specific and unique for prostate cancer AR-positive cell lines and corresponds with its ability to stimulate AR-SMRT complex formation. We suggest that AR and SMRT/N-CoR corepressors may form a stable complex in vitro and NaB may facilitate the interaction between AR nuclear steroid receptor and SMRT corepressor prote.
- MeSH
- androgenní receptory metabolismus MeSH
- butyráty farmakologie MeSH
- histondeacetylasa 2 analýza MeSH
- histondeacetylasy analýza metabolismus MeSH
- inhibitory histondeacetylas terapeutické užití MeSH
- korepresor 1 jaderného receptoru metabolismus MeSH
- kyseliny hydroxamové farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty farmakoterapie metabolismus MeSH
- promotorové oblasti (genetika) MeSH
- prostatický specifický antigen genetika MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
E-cadherin (E-CD) je pro epitel specifická adhezní molekula, jejíž exprese se, na rozdíl od invaziv- ních duktálních karcinomů, snižuje nebo zcela ztrácí u invazivních lobulárních karcinomů. O tyro- zin kináze c-erbB-2/HER-2/neu je známo, že může expresi adhezního systému, jehož součástí je E- CD, narušit. Vyšetřili jsme 106 případů málo diferencovaných (G2-G3) invazivních karcinomů prsu, z toho 91 IDC, 12 ILC a 3 pleomorfní lobulární karcinomy (PLC). Provedli jsme imunohistochemic- ké barvení estrogenového a progesteronového receptoru (ER/PR), Ki-67, E-CD a c-erbB-2/HER- 2/neu a vyšetřili amplifikaci genu pro c-erbB-2/HER-2/neu pomocí fluorescenční in situ hybridiza- ce. Amplifikace genu pro c-erbB-2/HER-2/neu byla pozorována u 55/91 (60,4 %) IDC, 3/12 (25 %) ILC a 1/3 (33,3 %) PLC a byla asociována s pozitivitou axilárních lymfatických uzlin. Ke ztrátě exprese E-CD došlo u 14/91 (15,4%) IDC, 10/12 (83,3 %) ILC a 2/3 (66,7 %) PLC. Ztráta imunoreaktivity E-CD v IDC byla asociována s amplifikací genu pro c-erbB-2/HER-2/neu, negativitou ER/PR a pozitivní- mi lymfatickými uzlinami, zatímco ILC s pozitivním E-CD byly obvykle HER-2/neu pozitivní. Exprese E-CD má pravděpodobné odlišný biologický význam v málo diferencovaných IDC a ILC. Signální dráha c-erbB-2/HER-2/neu může ovlivnit expresi E-CD ve většině invazivních duktálních karcinomech prsu in vivo.
E-cadherin (E-CD) is an epithelial-specific cell adhesion molecule, whose expression is lost in invasive lobular (ILC) but not in invasive ductal carcinoma (IDC) of the breast. This cell adhesion system can be disrupted by tyrosine kinase c-erbB-2/HER-2/neu. We examined 106 cases of high- grade invasive breast cancer, including 91 IDCs, 12 ILCs and 3 pleomorphic lobular carcinomas (PLCs). We determined Nottingham histological grade and performed immunohistochemistry for estrogen and progesterone receptors (ER/PR), Ki-67, E-CD and c-erbB-2/HER-2/neu with subsequent fluorescence in situ hybridization. Amplification of c-erbB-2/HER-2/neu gene was observed in 55/91 (60.4%) of IDCs, 3/12 (25%) of ILCs and 1/3 (33.3%) of PLCs, and associated with positive axillary lymph nodes. E-CD expression was lost in 14/91 (15.4%) of IDCs, 10/12 (83.3%) of ILCs and 2/3 (66.7%) of PLCs. The loss of E-CD immunoreactivity in IDCs appeared to be associated with c-erbB-2/HER-2/neu gene amplification, negative ER/PR status and positive lymph nodes, whereas E-CD-positive ILCs tended to be HER-2/neu-positive. The biological significance of E-CD expression seems to be different in high-grade IDC and ILC. Oncogenic pathway mediated by c- erbB-2/HER-2/neu may affect the E-CD expression in most invasive ductal breast carcinomas in vivo.
The paper continues in the previous experiment indicating a possible control of glycosylation and differentiation processes in the in vitro cultured tumor cells using suitable types of saccharides in the culture medium. In this experiment the effect of lactose, L-fucose, D-glucose, and D-galactose was studied. To determine glycosylative changes the panel of six lectins with various sugar specificity was used. The obtained results indicate that a specific sugar may significantly affect not only the growth of cells but also glycosylation processes, including cell differentiation.
- MeSH
- buněčné dělení účinky léků MeSH
- buněčné linie MeSH
- glykokonjugáty analýza metabolismus MeSH
- glykosylace MeSH
- hexosy farmakologie MeSH
- lektiny MeSH
- lidé MeSH
- nádory prsu MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
