Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3
Animals ; Hippocampus ; Long-Term Potentiation ; Mice ; Neuronal Plasticity ; Nuclear Receptor Coactivator 3/genetics* ; Synapses

OBJECTIVETo investigate the expression and amplification of steroid receptor coactivator- 3(SRC- 3) gene in colorectal carcinoma (CRC) and its clinicopathological significance.

METHODSImmunohistochemistry and fluorescence in situ hybridization (FISH) were used to detect the expression and amplification of SRC- 3 gene in CRC, and its association with patient's clinical pathological features was analyzed.

RESULTSA total of 60 patients with CRC were studied. SAR- 3 proteins were overexpressed in 23 cases (38% ). There was a significant association between SAR- 3 overexpression and neoplasm staging (P< 0.01). SRC- 3 protein was overexpressed in 62% of patients with Dukes C or D stage, whereas SRC- 3 protein was normally expressed in 74% of patients with Dukes A or B stage. As for FISH study, 47 cases were informative. High- level amplification of SRC- 3 gene was detected in 6 cases(13% ) and all showed overexpression of SRC- 3 protein. Low- level amplification of SRC- 3 was observed in 9 cases (19% ). Overexpression of SRC- 3 was detected in 6 cases. The remaining 9 of 32 patients(28% ) without amplification of SRC- 3 gene were observed with overexpression of SRC- 3 protein. In addition, 91% patients with CRC were found overexpression of SRC- 3 as well as overexpression of P53.

CONCLUSIONThe abnormal expression of SRC- 3 gene might impact on the function of P53 and development of CRC. There might exist some unknown mechanisms other than gene amplification of SRC- 3 to regulate its encoded protein expression in CRC.

Biomarkers, Tumor ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Gene Expression ; Histone Acetyltransferases ; genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Nuclear Receptor Coactivator 3 ; Trans-Activators ; genetics

OBJECTIVETo explore the possible mechanism of the inhibitory effect of liver X receptor alpha (LXRalpha) on lipopolysaccharide (LPS)-induced inflammation in mouse Kupffer cells (KCs).

METHODSThe KCs isolated from the liver of male KM mice and cultured in RPMI 1640 containing 20% FBS for 24 h were divided into control, LPS, T0901317, and LPS+T0901317 groups with corresponding treatments. The expressions of LXRalpha, interferon regulatory factor 3 (IRF3) and glucocorticoid receptor interacting protein 1 (GRIP1) in the KCs were detected by Western blotting. The levels of interferon beta (IFNbeta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe level of LXRalpha protein was highest in T0901317 group and lowest in LPS group, and was significantly higher in LPS+T0901317 group than in LPS group but lower than in T0901317 group (P<0.05). The levels of IRF3 and GRIP1 protein were the highest in LPS group, and significantly lowered by T0901317 treatment (P<0.05). The expression of IRF3 and GRIP1 proteins in LPS group and LPS+ T0901317 group were significantly higher than those in the control and T0901317 groups (P<0.05). The concentration of IFN-beta was significantly higher in LPS group than in the control and T0901317 group (P<0.05), and decreased in LPS+T0901317 group in comparison with that in LPS group (P<0.05). IFN-beta was the lowest in T0901317 group. The levels of TNF-alpha and IL-1beta were the highest in LPS group (P<0.05), and comparable between the other 3 groups (P>0.05).

CONCLUSIONPre-treatment with T0901317 before LPS stimulation can suppress the expressions of IRF3 and GRIP1 to inhibit the inflammation and hence Kupffer cell activation.

Animals ; Cells, Cultured ; Hydrocarbons, Fluorinated ; pharmacology ; Inflammation ; chemically induced ; Interferon Regulatory Factor-3 ; metabolism ; Kupffer Cells ; cytology ; metabolism ; Lipopolysaccharides ; pharmacology ; Liver X Receptors ; Male ; Mice ; Nuclear Receptor Coactivator 2 ; metabolism ; Orphan Nuclear Receptors ; physiology ; Sulfonamides ; pharmacology

OBJECTIVETo investigate the role of AIB1 gene in the development of esophageal squamous cell carcinoma (ESCC) and its clinicopathologic significance.

METHODSTwo tissue microarrays, including 203 cases of ESCC, were prepared. Fluorescence in-situ hybridization (FISH) and immunohistochemistry were performed to detect the amplification of AIB1 gene and expression of its encoded protein in ESCC. The results were correlated with various clinicopathologic parameters.

RESULTSIn the 203 cases of ESCC studied, FISH was successful in 115 cases. Amongst those, amplification/gain of AIB1 gene was observed in 15 cases, including high-level amplification in 5 cases (4.3%) and low-level gain in 10 cases (8.7%). As for immunohistochemical study, AIB1 protein was overexpressed in 94 cases of ESCC. There was a significant association of AIB1 overexpression and tumor staging. AIB1 was overexpressed in 66 of the 123 cases in advanced T stages (T3 to 4), compared with 25 of the 80 cases in early T stages (P = 0.008). Those cases with high-level amplification of AIB1 also showed overexpression of its encoded protein. On the other hand, 8 of the 10 cases with low-level gain of AIB1 showed protein overexpression. The remaining 41 of the 100 cases which did not have AIB1 gene amplification/gain demonstrated overexpression of AIB1 protein.

CONCLUSIONOverexpression of AIB1 protein caused by gene amplification/gain or other molecular mechanisms may play an important role in the development and/or progression of a subset of ESCC.

Carcinoma, Squamous Cell ; genetics ; pathology ; Cell Movement ; genetics ; Disease Progression ; Esophageal Neoplasms ; genetics ; pathology ; Female ; Gene Amplification ; Histone Acetyltransferases ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; methods ; Lymphatic Metastasis ; pathology ; Male ; Neoplasm Staging ; Nuclear Receptor Coactivator 3 ; genetics ; metabolism ; Tumor Cells, Cultured

OBJECTIVETo investigate the effects of gambogic acid (GA) on the proliferation inhibition and apoptosis induction in Human lung adenocarcinoma A549 cells in vitro, as well as the regulation of steroid receptor coactivator-3 (SRC-3) to explore the relationship between them.

METHODSThe effect of GA on the growth of A549 cells was studied by MTT assay. Apoptosis was detected by Hoechst 33258 staining. The localization of SRC-3 was determined by confocal laser scanning microscopy. Western blot and RT-PCR technique were applied to assess the expression of SRC-3.

RESULTSGA presented a striking proliferation inhibition potency on A549 cells in vitro, as well as apoptosis induction activity in a time- and dose-dependent manner. The IC(50) value for 24 h was (3.17 +/- 0.13) micromol/L. Overexpression of SRC-3 was found in A549 cells, whereas the SRC-3 protein and mRNA expression levels were significantly downregulated in A549 cells induced by GA in a dose-dependent manner. The location of SRC-3 was situated mainly in the cell nuclei.

CONCLUSIONGA exhibits a potent proliferation inhibition and apoptosis induction in human lung adenocarcinoma A549 cells, which might correspond to the downregulation of the expression of SRC-3. Thus, it promises to be a new target drug for lung cancer treatment.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Nucleus ; metabolism ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Nuclear Receptor Coactivator 3 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Xanthones ; administration & dosage ; pharmacology