ABSTRACT
Heat shock protein 27 (HSP27) is an important member of the heat shock protein family. In addition to its well-known chaperone function, recent studies have shown that it has been expressed in some malignant tumors. A large number of studies have shown that there is a significant correlation between HSP27 and thyroid carcinoma. This article reviews the research progress of HSP27 in thyroid carcinoma.
ABSTRACT
Heat shock protein 27 (HSP27) is an important member of the heat shock protein family.In addition to its well-known chaperone function,recent studies have shown that it has been expressed in some malignant tumors.A large number of studies have shown that there is a significant correlation between HSP27 and thyroid carcinoma.This article reviews the research progress of HSP27 in thyroid carcinoma.
ABSTRACT
Objective: To investigate the expression of heat shock protein 27 (HSP27) in multiple myeloma (MM) cells, and to explore its relationship with bortezomib (BTZ) resistance. Methods: The expression levels of HSP27 mRNA and protein in myeloma cells (CD38+/CD138+ plasma cells) of 22 patients with MM (12 newly treated patients and 10 relapsed patients after BTZ treatment) were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The BTZresistant U266/BTZ cell line was established, and CCK-8 assay was used to detect the effects of different concentrations of BTZ, doxorubicin and etoposide on the proliferation of U266/BTZ cells and the parent U266 cells. The expression levels of HSP27 mRNA and protein in U266/BTZ cells and U266 cells were also examined by real-time fluorescent quantitative PCR and Western blotting, respectively. The specific small interfering RNA (siRNA) was used to silence HSP 27 gene expression in U266/BTZ cells, and the impact of silencing HSP 27 gene expression on BTZ-induced apoptosis of U266/BTZ cells was assessed by FCM. Additionally, the U266 cells were treated with BTZ alone or in combination with p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor SB203580, then the expression levels of HSP27, phospho-HSP27 (p-HSP27), p38 MAPK, and p-p38 MAPK were measured by Western blotting. Finally, the recombinant lentivirus pCDH-CMV-MCS-EF1-copGFP-T2A-Puro/ HSP27 was constructed and infected into U266 cells to induce the overexpression of HSP 27 gene, then the activity of 20S proteasome in U266 cells with HSP 27 gene overexpression after treatment with different concentrations of BTZ was determined by fluorescence substrate method. Results: The expression levels of HSP27 mRNA and protein in myeloma cells from MM-relapsed patients were significantly higher than those in newly treated patients (both P < 0.01). BTZ-resistant myeloma cell line was successfully established, the half-maximal inhibitory concentration (IC50) of BTZ, doxorubicin and etoposide in BTZ-resistant U266/BTZ cells was significantly increased as compared with its parent U266 cells (all P < 0.01). The expressions of HSP27 mRNA and protein in U266/BTZ cells were significantly up-regulated (both P < 0.01). Silencing HSP 27 gene expression significantly increased BTZ-induced apoptotic rate of U266/BTZ cells (P < 0.01). Treatment with BTZ alone considerably up-regulated the expressions of HSP27, p-HSP27 and p-p38 MAPK in U266 cells, while this effect could be dramatically counteracted by pre-treatment with SB203580 (all P < 0.01). Furthermore, the overexpression of HSP 27 gene significantly reduced the inhibitory effects of BTZ at different concentrations on the activity of 20S proteasome in U266 cells (P < 0.01). Conclusion: The expression of HSP27 is closely related to BTZ-resistance of MM cells, which may be related to the BTZ exposure activating the p38 MAPK signaling pathway and up-regulating HSP27 expression, consequently decreasing the inhibitory effect of BTZ on proteasome activity through a feedback mechanism.
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Objective To investigate whether chemokine CC motif 2 (CCL2) is involved in the high residual platelet response,and the mechanism of CCL2 being involved in the regulation of platelets.Methods Forty patients with ST elevation myocardial infarction (STEMI) were admitted.P2Y12 reaction unit (PRU) was detected by VerifyNow.Forty patients were divided into high platelet reactivity group (high reactivity group,n=24) and normal platelet reactivity group (normal reactivity group,n=16) according to the results of PRU detection.Plasma CCL2 concentration of the STEMI patients was examined by ELISA.The expressions of CCL2 and CCR2 in the platelets were detected by Western blotting.After CCL2 stimulation,the kinases of which phosphorylation was changed in the platelets were screened by ARY003B protein chips.The phosphorylation of p38MAPK and HSP27 in the platelets was tested by Western blotting after CCL2 stimulation in the presence or absence of CCR2 antagonist (RS 102895) or p38MAPK signal pathway inhibitor (SB 203580).Results The plasma CCL2 concentration of high reactivity group was markedly higher than that of normal reactivity group.Moreover,compared with normal reactivity group,the expressions of CCL2 and CCR2 in the platelets of high reactivity group significantly increased.After the platelets were stimulated by CCL2,the phosphorylation of p38α and HSP27 enhanced in the platelets by protein chips screening.When RS 102895 or SB 203580 was treated before CCL2 stimulation,the phosphorylation of p38MAPK and HSP27 decreased.Conclusions CCL2 participates in high residual platelet response in an autocrine/paracrine way.CCL2/CCR2 might affect the function ofplatelets through p38MAPKHSP27 signal pathway.
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ObjectiveTo investigate the possible mechanism of common bile duct ligation (CBDL) preconditioning alleviating subsequent renal ischemia/reperfusion injury.MethodsC57BL/6 mice was divided into 3 groups.In CBDL group,the common bile duct was transiently ligated at day 0 (d0),and recanalized after two days (d2) and two days later (d4). Unilateral renal ischemia/reperfusion injury was performed.Sham operation was done in Sham group at d0,then unilateral renal I/R was performed at d4. Control group was set as normal contrast. Total bilirubin (TB) was monitored.24 h after I/R (d5),we collected blood to detect creatinine (Cr),and the expression of heat-shock protein 27 (HSP-27) and endothelial nitric oxide synthase (eNOS) was monitored by Western blotting at d0,d2,d4,d5 four time points.ResultsAfter CBDL,TB fell to normal at d4.Cr levels in CBDL group were lower than in Sham group (P＜0.05),the protein expression levels of HSP-27 and eNOS were increased from d2 and sustained to d5 in CBDL group as compared with Sham group ( P ＜ 0.05 ).Conclusion CBDL preconditioning can obviously alleviate renal ischemia/reoerfusion injury in mice probably by up-regulating the expression of HSP-27 and eNOS.
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PURPOSE: Heat shock protein 27 (HSP27) is induced by heat shock and other pathophysiologic stresses. We examined the relationship between HSP27 expression and Gleason score and pathologic stage of prostate cancer. MATERIALS AND METHODS: Fifty-three men were treated by radical prostatectomy for prostate cancer diagnosed from May 2004 to April 2007. Prostate tissues (n=53) were obtained from radical prostatectomy specimens of prostate cancer. The overall percentage of cancer cells showing staining (0% to 100%) was indicated by visual scoring. Specimens were graded from +1 to +3 intensity representing the range of staining area, for which below 5% is +1 grade, 5-50% is +2 grade, over 50% is +3 grade and focal reaction is +0.5 grade. RESULTS: An HSP27-positive reaction was seen in 2 of 11 cases (18.2%) with a Gleason score of 4-6, 11 of 19 cases (57.9%) with a Gleason score 7, 6 of 10 cases (60.0%) with a Gleason score 8, 12 of 13 cases (92.3%) with a Gleason score of 9 (p=0.001); the mean HSP27 reaction scores were 0.27, 0.86, 0.83, and 1.54 respectively (p=0.006). An HSP27-positive reaction was seen in 17 of 37 cases (46.0%) with pathologic stage T2, 10 of 12 cases (83.3%) with pathologic stage T3, and 4 of 4 cases (100%) with pathologic stage T4 (p=0.0032); the mean HSP27 reaction scores were 0.64, 1.17, and 2, respectively (p=0.007). HSP27 expression was not statistically significant according to age. CONCLUSIONS: There is correlation between HSP27 expression and Gleason score, pathologic stage of prostate cancer.