ライフサイエンスコーパス: maspin

1 cells to allow the incorporation of secreted Maspin.

2 rostate cancer cell lines, and with purified maspin.

3 expression of PC markers hepsin, AMACR, and maspin.

4 key event for this increase in apoptosis by maspin.

5 maspin and is dependent on the RSL region of maspin.

6 al role of Bax in the proapoptotic effect of maspin.

7 strong predominantly nuclear localization of maspin.

8 ilitating the increased adhesion function of maspin.

9 or the localization and adhesion function of maspin.

10 action between IRF6 and the tumor suppressor maspin.

11 l proliferation by 20-30% in the presence of maspin.

12 We noted that maspin (a) colocalized with uPA and uPA receptor (uPAR),

13 This leads to repression of maspin, a critical suppressor of metastasis, and thus co

14 g increase in mRNA and protein expression of maspin, a member of serine protease inhibitor family and

15 Maspin, a member of the serine protease inhibitor (serpi

16 Maspin, a non-inhibitory serpin, plays an important role

17 Maspin, a noninhibitory serine protease inhibitor, exert

18 Maspin, a novel serine protease inhibitor, suppresses tu

19 Maspin, a serine protease inhibitor (serpin), can suppre

20 tudy, we examined the unique relationship of maspin, a serine protease inhibitor (serpin), that plays

21 Previously, we showed that maspin, a serine protease inhibitor, specifically inhibi

22 response to apoptotic stimuli, we found that maspin-a noninhibitory member of the serine protease inh

23 Neutralizing antibody against maspin abrogated this effect of conditioned media.

24 An R340Q mutant retained full maspin activity; however, an R340A mutant lost activity.

25 Concomitantly, we showed that maspin acts as a negative regulator of this process.

26 Here, we provide evidence that maspin acts as a reactive oxygen species (ROS) scavenger

27 We report that maspin acts in the early steps in the cell adhesion proc

28 These results indicated that maspin affects cell adhesion and cytoskeleton reorganiza

29 We conclude that deletion of maspin affects VE function by reducing cell proliferatio

30 Consistently, maspin also correlates with increased expression of Bax

31 This study investigated the effect of maspin, an extracellular matrix (ECM) tumor suppressor,

32 Maspin, an ov-serpin, inhibits tumor invasion and induce

33 mediated apoptosis, and the presence of both maspin and Bax accelerated the apoptosis process.

34 The link between maspin and Bax up-regulation explains the loss of maspin

35 cer cells infected with wt p53 revealed both MASPIN and desmocollin 3 (DSC3) to be p53-target genes,

36 o its consensus DNA-binding sites within the MASPIN and DSC3 promoters, stimulating histone acetylati

37 correlated with particular Ets factors (e.g. maspin and Ese2), suggesting specific in vivo regulatory

38 intracellular interaction between endogenous maspin and GST correlated with an elevated total GST act

39 ts into the tumour suppressive properties of maspin and inform the development of novel cancer therap

40 spin and suggest an interactive role between maspin and IRF6 in regulating cellular phenotype, the lo

41 poptotic effect is mediated by intracellular maspin and is dependent on the RSL region of maspin.

42 Our results indicate that secretion of Maspin and its deposition into the extracellular milieu

43 In addition, the use of exosites by maspin and plasminogen activator inhibitor-1 to indirect

44 Both endogenously expressed maspin and purified maspin inhibited HDAC1.

45 en methylation and mRNA expression level for maspin and S100P in a large panel of pancreatic cancer c

46 tatin A resulted in synergistic induction of maspin and S100P mRNA in MiaPaCa2 cells where both genes

47 tion analysis, and two cancer-related genes, maspin and S100P, were found to be aberrantly hypomethyl

48 elp to elucidate the molecular mechanisms of maspin and suggest an interactive role between maspin an

49 veal a novel mechanism for tumor suppressive maspin and suggest that maspin may be used as a modifier

50 nt difference in the methylation patterns of maspin and two previously identified hypomethylated gene

51 In addition, a maspin antibody specifically blocked normal EB formation

52 sis, we identified the tumor suppressor gene maspin as a transforming growth factor beta (TGFbeta) ta

53 In the absence of Maspin, as is the case with most cancer cells, matrix de

54 g, suggesting that PAR1 negatively regulates Maspin at the transcriptional level.

55 ts in cell cycle arrest, and the presence of maspin augments this response.

56 functional pathways of maspin, we employed a maspin-baited yeast two-hybrid system and subsequently i

57 These findings will be useful for maspin-based therapeutic interventions against breast ca

58 d binding, suggesting the RSL is involved in maspin binding to cells.

59 cardiolipin in cells significantly prevents maspin binding to the inner mitochondrial membrane and d

60 d Interferon Regulatory Factor 6 (IRF6) as a maspin-binding protein.

61 terferometry assay revealed that recombinant maspin binds cardiolipin with an apparent K(d),of ~15.8

62 Maspin binds to cardiolipin in mitochondria and triggers

63 We propose a model of apoptosis in which maspin binds to cardiolipin, displaces cytochrome c from

64 Maspin bound specifically to the surface of the mammary

65 tumor cells treated with purified wild type maspin, but not Mas(R340A), enhanced cellular GST activi

66 nal region retained activity, suggesting the maspin C-terminal polypeptide is not required.

67 proteinase active site, with the result that maspin can bind to S195A tPA that is already complexed t

68 enous fluorescence, we demonstrate here that maspin can bind uPA and tPA in both single-chain and dou

69 s is the first report that a partial loss of maspin caused an early developmental defect of the prost

70 To this end, we used a full-length maspin cDNA bait to screen against both a primary prosta

71 DU-145-maspin cells exhibited higher sensitivity to doxazosin a

72 nificant increase in apoptosis in the DU-145 maspin cells, compared to DU-145 neo-transfectants witho

73 Binding is at an exosite on maspin close to, but outside of, the reactive center loo

74 A hydrophobic, lysine-rich domain in maspin consists of 27 aa, is located at position 268-294

75 blocked normal EB formation, indicating that maspin controls the process through a cell surface event

76 In this capacity, Maspin could potentially regulate mammary tissue remodel

77 Furthermore, we showed that maspin directly increased endodermal cell adhesion to la

78 We further demonstrate that maspin directly induces endothelial cell apoptosis in vi

79 Although maspin does not directly inhibit urokinase-type plasmino

80 y have significance in the identification of maspin-driven therapeutic targeting in advanced metastat

81 etween aa 139 and aa 225 was responsible for maspin effect on adhesion.

82 The maspin effect on HDAC1 correlated with an increased sens

83 Furthermore, the maspin effect on ROS generation was completely abolished

84 This maspin effect was associated with increased and sustaine

85 e binding to pro-uPA but also diminished the maspin effects on pro-uPA cleavage and cell detachment.

86 The maspin effects on surface-associated uPA and uPAR requir

87 This study uncovers a mechanism by which maspin exerts its effect on EC adhesion and migration th

88 support our current working hypothesis that maspin exerts its tumor suppressive role, at least in pa

89 or-related apoptosis-inducing ligand, DU-145-maspin expressing cells undergo apoptosis, via poly(ADP-

90 Thus, maspin-expressing cells exhibit a more prominent actin c

91 A expression was significantly inhibited in maspin-expressing cells.

92 Maspin-expressing mammary tumors are more susceptible to

93 he effect of doxazosin on cell attachment of maspin-expressing prostate cancer cells was evaluated on

94 In this article, we showed that maspin-expressing transfectant cells derived from PC cel

95 n and Bax up-regulation explains the loss of maspin-expressing tumor cells in invasive breast and pro

96 Furthermore, the maspin-expressing tumors contained significant fibrosis

97 relates with metastatic progression, reduced Maspin expression and infiltration of prostate tumours w

98 cal data regarding the predictive effects of maspin expression are variable.

99 These studies showed that maspin expression decreased tumor growth, reduced osteol

100 Maspin expression in cancer cell lines also correlated w

101 knockdown of G9A and DNMT1 led to increased MASPIN expression in MDA-MB-231 cells, to levels that we

102 tion by RANK ligand (RANKL/TNFSF11) inhibits Maspin expression in prostate epithelial cells, whereas

103 in vivo and that the extent and intensity of maspin expression in the skin is significantly (P = 0.01

104 Maspin expression is associated with better differentiat

105 Functionally, Maspin expression reduced the invasive capability of mel

106 potent antagonist of mutated ARs and induces maspin expression through AR.

107 his study, we showed that homozygous loss of maspin expression was lethal at the peri-implantation st

108 umor suppressor pathways in the induction of Maspin expression, thus leading to inhibition of cell mi

109 7 cells and that NO is capable of regulating maspin expression.

110 and c-Jun to the Maspin promoter and higher Maspin expression.

111 ple protein networks and a new hypothesis of maspin function based on the regulation of proteasome fu

112 Here, we analyzed maspin function in cell adhesion in nontransformed mamma

113 ts to characterize the mechanism(s) by which maspin functions as a tumor suppressor, its molecular ch

114 tance of the reactive center loop in certain maspin functions, despite the inability of maspin to dir

115 We report that loss of one copy of maspin gene in Mp(+/-) heterozygous knockout mice leads

116 We confirmed the maspin/GST interaction using purified proteins, human ep

117 expression but also increased intracellular maspin/GST interaction, which was inversely correlated w

118 Although purified maspin had no effect on the activity of purified GST in

119 ous knockout mice to determine the effect of maspin haploinsufficiency on prostate development and tu

120 Maspin has been identified as a potent angiogenesis inhi

121 Maspin has been shown to reduce cell migration, invasion

122 ; however, the fate and function of secreted Maspin has remained mostly unexplored.

123 another maspin partner) was detected in the maspin/HDAC1 complex.

124 In this study, we confirmed the maspin/HDAC1 interaction in human prostate tissues, in p

125 In this study, we have used maspin heterozygous knockout mice to determine the effec

126 is the first attempt to model the effect of maspin in a computational model to verify in vitro data.

127 nhibitor blocked the sensitization effect of maspin in a dose-dependent and time-dependent manner, de

128 was significantly decreased after expressing Maspin in a metastatic melanoma cell line.

129 ne deacetylation, was shown to interact with maspin in a yeast two-hybrid screening.

130 l cells and that it directly associates with maspin in a yeast two-hybrid system and in vitro.

131 One ATF was able to re-activate maspin in cell lines that comprise a maspin promoter sil

132 s identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites

133 etween endothelial nitric oxide synthase and maspin in MCF-7 cells and that NO is capable of regulati

134 gulation and function of IRF6 in relation to maspin in normal mammary epithelial cells.

135 to interrogate the therapeutic potential of Maspin in ovarian cancer.

136 Finally, knockdown of endogenous Maspin in p53 wild-type MCF10A/HER2 cells enhanced basal

137 Moreover, silencing Maspin in PAR-1-silenced cells reverted the inhibition o

138 entified a 40-fold increase in expression of Maspin in PAR-1-silenced metastatic melanoma cell lines.

139 , small interfering RNA (siRNA) silencing of maspin in PC3 cells increased HDAC activity.

140 Our findings implicate maspin in prostate cancer cell response to hypoxia via r

141 information regarding the molecular role of maspin in regulating mammary epithelial growth, remodeli

142 lular fractionation shows that a fraction of maspin (in both TM40D-Mp and mutant maspinDeltaN cells)

143 smooth muscle cells (PSMC), and recombinant maspin increased PSMC cell adhesion but inhibited cell p

144 is important for TS-IIA's antiandrogenic and maspin induction activities.

145 Stable transfection of Maspin inhibited basal and TGFbeta-stimulated MDA-MB-231

146 h endogenously expressed maspin and purified maspin inhibited HDAC1.

147 These data represent evidence that maspin inhibits PC-induced bone matrix remodeling and in

148 It is well documented that tumor suppressive maspin inhibits tumor cell invasion and extracellular ma

149 Our data indicate that maspin inhibits tumor progression through the mitochondr

150 Therefore, in an attempt to identify maspin-interacting proteins and thereby gain insight int

151 ral endoderm after implantation; deletion of maspin interfered with the formation of the endodermal c

152 We have shown that, similar to maspin, IRF6 expression is inversely correlated with bre

153 ight into the biological significance of the maspin-IRF6 interaction, we examined the regulation and

154 Maspin is a cytosolic, cell surface-associated, and secr

155 Maspin is a key tumor suppressor gene in prostate and br

156 Maspin is a mammary serine protease inhibitor or serpin

157 Maspin is a member of the serine protease inhibitor (ser

158 Maspin is a member of the serpin family with a reactive

159 Maspin is a multifaceted protein, regulating tumor cell

160 Maspin is a non-inhibitory serine protease inhibitor (se

161 Maspin is a serpin that exhibits antiangiogenic properti

162 Maspin is a tumor-suppressor serpin (serine protease inh

163 Maspin is a type II tumour metastasis suppressor which h

164 Maspin is a unique serpin with the ability to suppress c

165 In addition, we show that maspin is associated with detergent-insoluble cortical c

166 Expression of Maspin is decreased in primary tumors and lost in metast

167 range from 3 months to 84 years) showed that maspin is expressed by KCs in vivo and that the extent a

168 Maspin is highly expressed in normal mammary epithelial

169 We hypothesized that secreted Maspin is incorporated into the matrix deposited by norm

170 Expression of metastatic suppressor maspin is lost in advanced prostate cancer.

171 Maspin is mostly cytoplasmic and is partially secreted;

172 Collectively, these results suggest that maspin is part of the supramolecular structure of the ad

173 To our knowledge, maspin is the only proapoptotic serpin among all of the

174 ert a paracrine antiangiogenic activity, and maspin is the principal contributor to this potentially

175 versely both an antimaspin antibody (Ab) and maspin knockdown by RNA interference resulted in decreas

176 Conversely, maspin knockdown by small interfering RNA increased the

177 embryonic development in vivo, we generated maspin knockout mice by gene targeting.

178 ar endothelial cells are highly sensitive to maspin level inside the cells.

179 TGFbeta did not activate Maspin-luciferase reporter in p53-mutant MDA-MB-231 brea

180 Since its reported discovery in 1994, maspin (mammary serine protease inhibitor) has been char

181 n a recent report, we provided evidence that maspin may also suppress tumor progression by enhancing

182 or tumor suppressive maspin and suggest that maspin may be used as a modifier for apoptosis-based can

183 (uPA) activity, we have shown evidence that maspin may block the pericellular proteolysis mediated b

184 the pericellular uPA system and suggest that maspin may offer an opportunity to improve therapeutic i

185 ether, our data led to a new hypothesis that maspin may stabilize mature FACs by quenching localized

186 xpression of Bcl-2 protected the HUVECs from maspin-mediated apoptosis, and the presence of both masp

187 itor, indicating an essential role of GST in maspin-mediated cellular response to oxidative stress.

188 This may occur through maspin-mediated inhibition of pericellular proteolysis.

189 s study we determined the mechanism by which maspin mediates increased MCF10A cell adhesion.

190 Despite this there are reports that maspin might regulate uPA-dependent processes in vivo.

191 The diversity of the effects of maspin motivated us to develop an intelligent model to i

192 Maspin (Mp) is a member of the serpin family with inhibi

193 Furthermore, a COOH-terminally truncated maspin mutant, which bound to HDAC1 but not GST, did not

194 In this study, we examined the effect of maspin on endothelial cell (EC) adhesion and migration i

195 sis that the endogenous inhibitory effect of maspin on HDAC1 is coupled with glutathione-based protei

196 vidence that support an inhibitory effect of maspin on HDAC1 through direct molecular interaction, wh

197 r the first time the far reaching effects of maspin on multiple protein networks and a new hypothesis

198 To test the effect of tumor-associated maspin on PC-induced bone matrix remodeling and tumor gr

199 growth in order to investigate the impact of maspin on the growth and evolutionary dynamics of the ca

200 The response of maspin-overexpressing clones of human prostate cancer ce

201 s within a hypoxic microenvironment, we used maspin-overexpressing DU-145 human prostate cancer cells

202 Suppression of maspin overexpression by RNA interference desensitizes c

203 Maspin overexpression in prostate cancer cells resulted

204 In this report, we show that when maspin overexpression is targeted in vivo to endothelial

205 In this study, we investigated the effect of maspin overexpression on the apoptotic/antiadhesion resp

206 d cathepsin E (P < 0.001), Plk1 (P = 0.021), maspin (P = 0.001), and survivin (P = 0.001) as independ

207 Interestingly, substitution of maspin p1' site Arg340 in the reactive site loop (RSL) w

208 Re-expression of maspin partially rescued the defects observed in the Mp(

209 gly, glutathione S-transferase (GST, another maspin partner) was detected in the maspin/HDAC1 complex

210 ort, we found the expression of cathepsin E, maspin, Plk1, and survivin to be significantly associate

211 ue of the protein expression of cathepsin E, maspin, polo-like kinase 1 (Plk1), and survivin in patie

212 Maspin promoter activity was significantly increased aft

213 increased binding of Ets-1 and c-Jun to the Maspin promoter and higher Maspin expression.

214 ranscription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines

215 ed the presence of both Smads and p53 at the Maspin promoter in TGFbeta-treated cells, suggesting tha

216 ctivate maspin in cell lines that comprise a maspin promoter silenced by epigenetic mechanisms.

217 Ets-1 and c-Jun transcription factors to the Maspin promoter, both known to activate Maspin transcrip

218 ed association of Smad2/3 with a transfected Maspin promoter.

219 ction and intact p53-binding elements in the Maspin promoter.

220 st 18-base pair (bp) unique sequences in the maspin promoter.

221 revealed an exceptional specificity for the Maspin promoter.

222 which exhibit methylation of the endogenous Maspin promoter.

223 Only the PSA and maspin promoters have been identified as targets of this

224 a model in which IRF6, in collaboration with maspin, promotes mammary epithelial cell differentiation

225 o engage in additional, as yet unidentified, maspin-protein interactions that may serve to regulate t

226 Addition of recombinant maspin rapidly increased MCF-10A cell adhesion to the en

227 er cell growth in nude mice accompanied with Maspin re-expression in the treated tumors.

228 Importantly, DSC3 and MASPIN reactivation was closely and consistently linked

229 Results show that maspin reduces migration by 10-40%, confirmed by publish

230 for activity suggests the mechanism by which maspin regulates cell-matrix adhesion and tumor cell inv

231 However, how maspin regulates prostate tumor progression is not fully

232 However, the molecular mechanism of maspin remains illusive, primarily because its molecular

233 et molecule(s), the modification of which by maspin renders tumor cells sensitive to chemotherapeutic

234 Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor in

235 Ablation of these cysteine residues in maspin resulted in a significant increase in total ROS p

236 Sufficiency of the maspin RSL for activity suggests the mechanism by which

237 These data show an important role of maspin RSL in regulating the uPA/uPAR-dependent cell det

238 The maspin RSL peptide inhibited binding, suggesting the RSL

239 To address molecular mechanisms underlying maspin's activity, we restored its expression in invasiv

240 Alteration to maspin's cardiolipin binding domain changes its ability

241 Whereas six of the genes (maspin, SCCA1, SCCA2, hurpin, megsin and pAI-2) were com

242 Antiangiogenic activity of maspin secreted by senescent KCs was investigated in vit

243 ax-mediated mitochondrial apoptotic pathway, maspin sensitized the apoptotic response of breast and p

244 INB2), MNEI (SERPINB1), PI-6 (SERPINB6), and maspin (SERPINB5) are highly conserved.

245 geted the Mammary Serine Protease Inhibitor (maspin) (SERPINB5) tumor suppressor, which is silenced b

246 cells containing a triple-cysteine mutant of maspin showed elevated ERK1/2 activity, a downstream tar

247 Maspin significantly enhanced HUVEC cell adhesion to var

248 In the current study, maspin significantly inhibited the Ca2+ reduction-induce

249 ratin 18 (CK18), and p21(WAF1/CIP1), whereas maspin siRNA decreased CK18 expression in PC3 cells.

250 cell apoptosis in vitro, and this effect is maspin specific.

251 mical and biophysical analyses revealed that maspin specifically bound to pro-uPA with a deduced K(d)

252 creases expression of the AR repression gene maspin, suggesting that Taxol treatment inhibits AR acti

253 Furthermore, maspin, survivin, and cathepsin E expression significant

254 racellular maspin targets, the extracellular maspin target(s) remains elusive.

255 e been identified as candidate intracellular maspin targets, the extracellular maspin target(s) remai

256 ated expression of the metastasis suppressor Maspin, the ablation of which restored metastatic activi

257 r, our data suggest a new mechanism by which maspin, through its direct interaction with GST, may inh

258 The ability of maspin to bind these proteinases without involvement of

259 n maspin functions, despite the inability of maspin to directly inhibit tPA or uPA catalytic activity

260 The present study supports the ability of maspin to enhance the apoptotic threshold of prostate ca

261 Intravascular administration of adenovirus-maspin to mice bearing mammary tumors disrupts tumor-ind

262 This translocation of maspin to the mitochondria is linked to the opening of t

263 To dissect the contribution of maspin to tumor cell responses within a hypoxic microenv

264 tate epithelial cells, whereas repression of Maspin transcription requires nuclear translocation of a

265 uclear IKKalpha activation and inhibition of Maspin transcription, thereby promoting the metastatic p

266 th transcription factors cooperate to induce Maspin transcription.

267 the Maspin promoter, both known to activate Maspin transcription.

268 downregulation of the 189 isoform of VEGF in maspin transfectants, while a fivefold induction of Smad

269 with a Bax-silencing small interfering RNA, maspin-transfected cells became significantly more resis

270 was more responsive to apoptosis stimuli in maspin-transfected cells than in the mock-transfected ce

271 Third, the apoptosis induction of maspin-transfected cells was associated with increased a

272 translocated from cytosol to mitochondria in maspin-transfected cells.

273 Accordingly, maspin-transfected DU145 cells exhibited increased expre

274 remodeling and tumor growth, we injected the maspin-transfected DU145 cells into human fetal bone fra

275 First, Bax was up-regulated in maspin-transfected prostate and breast tumor cells, wher

276 an indicator of focal adhesion disassembly, maspin-treated HUVECs had elevated FAK phosphorylation c

277 Analysis of HUVECs following maspin treatment revealed increased integrin-linked kina

278 stingly, tumor neovessels become leaky after maspin treatment, whereas normal mature vessels are not

279 as normal mature vessels are not affected by maspin treatment.

280 e decreased dramatically at 30 min following maspin treatment.

281 1 negatively regulates the expression of the Maspin tumor-suppressor gene in the acquisition of the m

282 rin co-immunoprecipitate, suggesting a novel maspin-uPA-uPAR-beta1 integrin mega-complex that regulat

283 Finally, we showed that maspin, uPAR, and beta1 integrin co-immunoprecipitate, s

284 To date, the whole cellular mechanisms that maspin uses to influence tumour cell behaviours have not

285 indings establish a novel mechanism by which maspin utilizes its cysteine thiols to inhibit oxidative

286 A maspin variant that has a point mutation of Arg(340) to

287 We showed that maspin was also expressed in prostate smooth muscle cell

288 ar, the adhesion-associated tumor suppressor maspin was differentially regulated by betaIII-tubulin.

289 We found that maspin was expressed in blood vessels ECs and human umbi

290 We found that although Maspin was expressed in some primary ovarian tumors, the

291 Maspin was found to be overexpressed in response to hypo

292 icantly more often in squamous cell tumours, maspin was identified as the most frequently over-repres

293 Maspin was specifically expressed in the visceral endode

294 gain insight into the functional pathways of maspin, we employed a maspin-baited yeast two-hybrid sys

295 ngiogenesis inhibitors, thrombospondin-1 and maspin, were lower compared to controls.

296 r suppressor genes, desmocollin 3 (DSC3) and MASPIN, which are frequently silenced in this manner in

297 fore, we have identified a novel property of maspin, which involves the control of the proliferation

298 Maspin with ovalbumin as the C-terminal region retained

299 ), and heat shock protein 70 interacted with maspin with the highest frequencies.

300 Strong nuclear expression of maspin within primary tumour cells is correlated with in