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Objective To investigate the effect of FBXW7 on the expression and localization of HSF1 in colorectal cancer cells. Methods The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 deletion (KO) and wild-type (WT) FBXW7-expressing counterpart colorectal cancer cells were detected by Western blot. The nucleoprotein expression and localization of pHSF1Ser326 in heat-shocked or recovery stage cells were observed by Western blot and immunofluorescence method. Results The HSF1 expression level in DLD1 cells transfected with FBXW7α was decreased significantly (P < 0.01). The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 KO cells were higher than those in WT cells (all P < 0.05). HSF1 and pHSF1Ser326 in FBXW7 KO cells were mainly expressed in nucleus and weakly expressed in cytoplasm. After warm stimulation, the expression of HSF1 and pHSF1Ser326 in WT cells recovered to the unstimulated level, while the expression of HSF1 and pHSF1Ser326 in FBXW7 KO cells were higher in the nucleus (all P < 0.01). Conclusion Loss of FBXW7 could affect the nuclear HSF1 recovery after warm stimulation. It may be associated with FBXW7 deletion inhibiting the degradation of nuclear HSF1.
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PURPOSE: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. MATERIALS AND METHODS: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. RESULTS: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). CONCLUSION: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.
Subject(s)
Humans , Dataset , Gene Expression , Heat-Shock Response , Hot Temperature , Kaplan-Meier Estimate , Oligonucleotide Array Sequence Analysis , Prognosis , Shock , Stomach NeoplasmsABSTRACT
ABSTRACT:Objective To test the expressions of heat shock transcription factor 1 (HSF1 )and XIAP-associated factor 1 (XAF1 )in different endometrial tissues,and analyze the association between their expressions and the clinicopathological features of this malignancy.Methods The expressions of HSF1 and XAF1 in 64 cases of endometria1 carcinoma (EC group)and 33 cases of normal endometrial tissues (NE group)were detected with immunohistochemistry S-P method.The correlation was observed.Results The positive expression rate of HSF1 was much higher in EC group than in NE group (76.6% vs .36.4%,P <0.05).The positive rate of XAF1 was 31.2% in EC group and 72.7% in NE group (P <0.05).The positive expressions of HSF1 and different subgroups of histological grade,myometrial invasion and lymph node metastasis were significantly different (P <0.05)in EC group.The positive expressions of XAF1 and different subgroups of histological grade,myometrial invasion,clinical stage and lymph node metastasis were significantly different (P < 0.05 )in EC group.There was a negative correlation between HSF1 and XAF1 in EC group (P <0.05).Conclusion In EC group,the high expression of HSF1 may inhibit the growth of XAF1 expression,cause excessive growth of cancer cells,reduce the apoptosis of cancer cells,and finally lead to the further development of tumors.
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Objective:To explore the regulatory effect of Hsf 1 on PLC/PRF5 hepatoma cells proliferation.Methods: By shRNA gene silencing technology ,constructed PLC/PRF5 hepatoma cell line of Hsf 1 gene silencing.To detect the expression of Hsf 1, p53 and Rb proteins in PLC/PRF5 hepatoma cells by Western blot.The proliferation of PLC/PRF5 cell line was observed by methylthiazolyl tetrazolium assay ( MTT ) , plate clone formation assay ( PCFA ) and cell cycle assay.Results: shRNA-Hsf1 could significantly inhibit the expression of Hsf 1 in PLC/PRF5 cells.It could induce PLC/PRF5 cells stopping at G1 phase of cell cycle , inhibit cell proliferation and colonal formation;silencing Hsf1 caused up-regulation of p53 and Rb proteins expression in PLC/PRF5 cells.Conclusion: Silencing Hsf1 is involved in up-regulation of p53 and Rb proteins expression , which results in inhibiting proliferation of PLC/PRF5 hepatoma cells.
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The Bis protein is known to be involved in a variety of cellular processes including apoptosis, migration, autophagy as well as protein quality control. Bis expression is induced in response to a number of types of stress, such as heat shock or a proteasome inhibitor via the activation of heat shock factor (HSF)1. We report herein that Bis expression is increased at the transcriptional level in HK-2 kidney tubular cells and A172 glioma cells by exposure to oxidative stress such as H2O2 treatment and oxygen-glucose deprivation, respectively. The pretreatment of HK-2 cells with N-acetyl cysteine, suppressed Bis induction. Furthermore, HSF1 silencing attenuated Bis expression that was induced by H2O2, accompaniedby increase in reactive oxygen species (ROS) accumulation. Using a series of deletion constructs of the bis gene promoter, two putative heat shock elements located in the proximal region of the bis gene promoter were found to be essential for the constitutive expression is as well as the inducible expression of Bis. Taken together, our results indicate that oxidative stress induces Bis expression at the transcriptional levels via activation of HSF1, which might confer an expansion of antioxidant capacity against pro-oxidant milieu. However, the possible role of the other cis-element in the induction of Bis remains to be determined.
Subject(s)
Apoptosis , Autophagy , Cysteine , Glioma , Hot Temperature , Kidney , Oxidative Stress , Proteasome Inhibitors , Quality Control , Reactive Oxygen Species , ShockABSTRACT
A variety of physical and chemical stimuli were known to cause specific stress response in all organisms. Research done over the past 25 years has shown that there is a striking uniformity in the manner in which organisms respond to different forms of stress. Expression of stress responsive genes was shown to be regulated by two or more specific transcription factors present in the cell prior to stress. These specific genes were also activated during development. In this review, the role of heat shock transcription factors in stress response, during development and during cell cycle is described.
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Aim To observe the effect of the polymerization of HSF1 on the febrile response in fever rabbits,and further to investigate HSF1 action in thermoregulation and the possible central mechanism.Methods 70 rabbits were divided randomly into 4 groups:the control group(N),the quercetin group(Q),the LPS-feverish group(L),the quercetin+LPS-feverish group(Q+L).Changes in body temperature were continually observed;the expression of HSF1 and HSP70 in hypothalamus was detected by Western blot;the content of AVP in hypothalamus and VSA was measured by radioimmunoassay.Results ① The sequence of the maximum change of temperature(△Tmax)from low to high:group Q