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

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

8 strong predominantly nuclear localization of maspin.

9 ilitating the increased adhesion function of maspin.

10 or the localization and adhesion function of maspin.

11 action between IRF6 and the tumor suppressor 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 Neutralizing antibody against maspin abrogated this effect of conditioned media.

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

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

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

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

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

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

29 Consistently, maspin also correlates with increased expression of Bax

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

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

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

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

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

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

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

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

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

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

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

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

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

43 Both endogenously expressed maspin and purified maspin inhibited HDAC1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

59 Maspin bound specifically to the surface of the mammary

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

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

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

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

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

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

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

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

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

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

70 itution of the RSL of ovalbumin with that of maspin converted inactive ovalbumin into a fully active

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

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

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

74 Although maspin does not directly inhibit urokinase-type plasmino

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

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

77 The maspin effect on HDAC1 correlated with an increased sens

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

79 This maspin effect was associated with increased and sustaine

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

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

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

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

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

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

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

87 Maspin-expressing mammary tumors are more susceptible to

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

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

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

91 Furthermore, the maspin-expressing tumors contained significant fibrosis

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

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

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

95 Maspin expression in cancer cell lines also correlated w

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

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

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

99 Maspin expression is associated with better differentiat

100 Functionally, Maspin expression reduced the invasive capability of mel

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

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

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

104 7 cells and that NO is capable of regulating maspin expression.

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

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

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

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

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

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

111 f the promoter of the tumor suppressor gene, MASPIN: Growth-suppressive effects of Pdef expression ar

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

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

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

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

116 Maspin has been identified as a potent angiogenesis inhi

117 Maspin has been shown to reduce cell migration, invasion

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

142 h endogenously expressed maspin and purified maspin inhibited HDAC1.

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

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

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

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

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

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

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

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

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

152 Maspin is a mammary serine protease inhibitor or serpin

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

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

155 Maspin is a multifaceted protein, regulating tumor cell

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

157 Maspin is a serpin that exhibits antiangiogenic properti

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

159 Maspin is a type II tumour metastasis suppressor which h

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

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

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

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

164 Maspin is highly expressed in normal mammary epithelial

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

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

167 Maspin is mostly cytoplasmic and is partially secreted;

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

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

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

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

172 Conversely, maspin knockdown by small interfering RNA increased the

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

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

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

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

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

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

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

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

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

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

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

184 ptide to characterize the role of the RSL in maspin-mediated functions.

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

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

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

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

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

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

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

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

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

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

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

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

197 Here, we use maspin/ovalbumin chimeric proteins and the maspin reacti

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

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

200 Suppression of maspin overexpression by RNA interference desensitizes c

201 Maspin overexpression in prostate cancer cells resulted

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

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

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

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

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

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

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

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

210 Maspin promoter activity was significantly increased aft

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

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

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

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

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

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

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

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

219 revealed an exceptional specificity for the Maspin promoter.

220 which exhibit methylation of the endogenous Maspin promoter.

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

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

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

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

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

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

227 e maspin/ovalbumin chimeric proteins and the maspin reactive site loop (RSL) peptide to characterize

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

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

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

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

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

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

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

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

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

237 The maspin RSL peptide inhibited binding, suggesting the RSL

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

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

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

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

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

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

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

245 Maspin significantly enhanced HUVEC cell adhesion to var

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

264 th transcription factors cooperate to induce Maspin transcription.

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

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

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

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

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

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

271 Accordingly, maspin-transfected DU145 cells exhibited increased expre

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

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

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

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

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

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

278 e decreased dramatically at 30 min following maspin treatment.

279 1 negatively regulates the expression of the Maspin tumor-suppressor gene in the acquisition of the m

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

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

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

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

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

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

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

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

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

289 Maspin was found to be overexpressed in response to hypo

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

291 The effect(s) of NO modulators on maspin was measured using reverse transcriptase-polymera

292 Maspin was specifically expressed in the visceral endode

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

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

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

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

297 Maspin with ovalbumin as the C-terminal region retained

298 us the C-terminal region or the RSL alone of maspin with that of ovalbumin resulted in the loss of th

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