The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from ...The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.展开更多
The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level r...The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase （GUS） fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C （PLC） inhibitors {1-[6-（（ 1713-3-Methoxyestra-1,3,5（10）-trien- 7-yl）amino）hexyl]-2,5-pyrrolidinedione } （U-73122）. The intracellular-free calcium ion concentration （[Ca^2＋]i） increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2＋]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.展开更多
The present study aims to explore the effects of p53 and its target gene Rap2B on the autophagy of U2OS cells.U2OS cells were treated with siRNA against p53,Rap2B,and PLCε.Relative expressions of p53,Rap2B,and PLCεw...The present study aims to explore the effects of p53 and its target gene Rap2B on the autophagy of U2OS cells.U2OS cells were treated with siRNA against p53,Rap2B,and PLCε.Relative expressions of p53,Rap2B,and PLCεwere determined using quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.Levels of IP3 in the cells were determined using Enzyme-linked Immunosorbent Assay(ELISA).Levels of Ca^(2+) were detected using Flow cytometry.Fluorescence microscopy was used to observe the autophagy of cells.Knockdown of p53 significantly decreased the expressions of Rap2B protein.Additionally,knockdown of p53 significantly decreased the mRNA levels of PLCε.The knockdown of p53,Rap2B,and PLCεsignificantly decreased the levels of intracellular IP3 and Ca^(2+) and promoted autophagy of U2OS cells.Our results demonstrated that p53-Rap2B-PLCε-IP3 signaling pathway regulated autophagy of U2OS cells.展开更多
AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was e...AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.展开更多
文摘The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.
基金This work was supported by the National Natural Science Foundation of China （No. 30270796） Natural Science Foundation of Hebei Province, China （No. C2005000171）.
文摘The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase （GUS） fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C （PLC） inhibitors {1-[6-（（ 1713-3-Methoxyestra-1,3,5（10）-trien- 7-yl）amino）hexyl]-2,5-pyrrolidinedione } （U-73122）. The intracellular-free calcium ion concentration （[Ca^2＋]i） increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2＋]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.
文摘The present study aims to explore the effects of p53 and its target gene Rap2B on the autophagy of U2OS cells.U2OS cells were treated with siRNA against p53,Rap2B,and PLCε.Relative expressions of p53,Rap2B,and PLCεwere determined using quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.Levels of IP3 in the cells were determined using Enzyme-linked Immunosorbent Assay(ELISA).Levels of Ca^(2+) were detected using Flow cytometry.Fluorescence microscopy was used to observe the autophagy of cells.Knockdown of p53 significantly decreased the expressions of Rap2B protein.Additionally,knockdown of p53 significantly decreased the mRNA levels of PLCε.The knockdown of p53,Rap2B,and PLCεsignificantly decreased the levels of intracellular IP3 and Ca^(2+) and promoted autophagy of U2OS cells.Our results demonstrated that p53-Rap2B-PLCε-IP3 signaling pathway regulated autophagy of U2OS cells.
文摘AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.
