The Human Myoepithelial Cell Exerts Antiproliferative Effects on Breast Carcinoma Cells Characterized by p21WAF1/CIP1Induction, G2/M Arrest, and Apoptosis

Shao, Zhi Ming; Nguyen, Mai; Alpaugh, Mary L.; O'Connell, Jerome T.; Barsky, Sanford H.

doi:10.1006/excr.1998.4066

Cited by 85 publications

(66 citation statements)

References 18 publications

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“…Furthermore, the apoptosis-sensitizing e ect of maspin appears to depend on its overall sequence. These data not only help explain the earlier observation that overexpression of maspin correlates with increased apoptosis under certain conditions (Li et al, 1998;Shao et al, 1998;Zhang et al, 1999Zhang et al, , 2000, but also provide exciting new leads regarding the complex tumor suppressive modes of maspin action.…”

Section: Discussionsupporting

confidence: 67%

“…The evidence that maspin expression correlates with increased sensitivity of mammary epithelial cells to apoptosis (Li et al, 1998;Shao et al, 1998;Zhang et al, 1999Zhang et al, , 2000 raised the possibility that the maspin e ect on tumor cell motility/ invasion may result from an increased cell apoptosis. To address this possibility, stable maspin transfectant clones derived from mammary carcinoma cells MDA-MB-435, Tn15 and Tn16, along with a mock transfectant clone pCIneo were ®rst examined in parallel by motility assay and by caspase-3 activity assay.…”

Section: Maspin Sensitizes Mda-mb-435 Cells To Staurosporineinduced Amentioning

confidence: 99%

“…It is important to bear in mind, however, that normal mammary epithelial cells that express high level of maspin do not undergo detectable apoptosis either in vivo or in vitro. Moreover, maspin neither alters the growth kinetics of a variety of breast epithelial cell lines, nor directly induces apoptosis in vitro (Shao et al, 1998;Sheng et al, 1994Sheng et al, , 1996. Thus, the maspin e ect on apoptosis may be a part of cellular response to speci®c pathological or pharmacological apoptotic stimuli.…”

Section: Introductionmentioning

confidence: 99%

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Maspin sensitizes breast carcinoma cells to induced apoptosis

et al. 2002

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Maspin, a novel serine protease inhibitor (serpin), suppresses the growth and metastasis of breast tumor in vivo. However, the underlying molecular mechanism is unclear. In the current study, we report the ®rst evidence that endogenous maspin expression in mammary carcinoma cells MDA-MB-435 enhanced staurosporine (STS)-induced apoptosis as judged by the increased fragmentation of DNA, increased proteolytic inactivation of poly-[ADP-ribose]-polymerase (PARP), as well as the increased activation of caspase-8 and caspase-3. In parallel, recombinant maspin did not directly regulate the proteolytic activities of either caspase-3 or caspase-8 in vitro. Consistent with this result, maspin expressing normal mammary epithelial cells underwent more rapid STS-induced apoptosis as compared to breast carcinoma cells. Interestingly, maspin transfectant cells did not undergo spontaneous apoptosis in the absence of STS. Moreover, neither puri®ed maspin protein added from outside nor endogenous maspin secreted to the cell culture media sensitized cells to STS-induced apoptosis. To investigate the structural determinants of maspin in its apoptosis-sensitizing e ect, MDA-MB-435 cells were also transfected with maspin/PAI-1 and PAI-1/maspin chimeric constructs resulting from swapping the Nterminal and the C-terminal domains between maspin and PAI-1 (plasminogen activator inhibitor type 1). The resulting stable transfectant clones expressing maspin/ PAI-1 and PAI-1/maspin, respectively, did not undergo spontaneous apoptosis, and were similarly inhibited as maspin transfectant cells in motility assay. Interestingly, however, expression of both maspin/PAI-1 and PAI-1/ maspin in MDA-MB-435 cells failed to sensitize these cells to STS-induced apoptosis. Taken together, our evidence provides new insights into the complex molecular mechanisms of maspin that may suppress breast tumor progression not only at the step of invasion and motility, but also by regulating tumor cell apoptosis. The sensitizing e ect of maspin on apoptosis is to be contrasted by the pro-survival e ect of several other serpins.

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Section: Discussionsupporting

confidence: 67%

Section: Maspin Sensitizes Mda-mb-435 Cells To Staurosporineinduced Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Maspin sensitizes breast carcinoma cells to induced apoptosis

et al. 2002

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“…Western blot with mouse monoclonal antibodies to HSV 1 -tk protein (Abcam Ltd, Cambridge, UK) diluted 1:500, was performed according to standard protocols. 19 Blot quantitation was performed with a Molecular Dynamics Laser Densitometer (Model PSD) and the Image Quant Version 1 software, and the normalization of protein loading was carried out with b-actin.…”

Section: Western Blot Analysismentioning

confidence: 99%

Enhanced efficiency and specificity of ovarian cancer gene therapy in rats with a novel nonviral gene delivery system (GE7) via intraovarian artery perfusion approach

et al. 2005

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Transfer of the herpes simplex virus type I-thymidine kinase gene, followed by the administration of ganciclovir (HSV 1 -tk/GCV) into ovarian cancer-derived cell line either in vitro or transplanted into nude mice has been shown to provide a potential strategy for the gene therapy of ovarian cancer. We investigated the antitumor effects of HSV 1 -tk/GCV strategy with a chemically induced rat ovarian cancer model and a tumor-selective gene delivery by a novel nonviral gene delivery system (GE7) through the ovarian artery and tail vein. We demonstrated the expression of a reporter gene, b-gal gene, as well as HSV 1 -tk gene in tumors and other organs, evaluated the overall antitumor effects after the GCV treatment and analyzed the tumor cell cycle phase distribution. Via the ovarian artery route, the expressions of b-gal and HSV 1 -tk in tumors were significantly stronger than those expressed in such organs as the hearts, livers, spleens, lungs and kidneys. However, no b-gal and HSV 1 -tk were detected in the tumor tissues when administrated via the tail vein, and little was found in other organs. The cell cycle analysis showed that the total S-phase of tumor cells in the test intra-arterial treatment group was considerably higher than that of the controls. The weight of the tumor tissues in the group treated by the intra-arterial route (4.0672.12 g) was much less than the group treated intravenously (18.2578.34 g) (Po.01). These findings indicated that the administration of GE7/HSV 1 -tk complex via the ovarian artery route could be a promising avenue of future human ovarian cancer treatment.

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“…The evidence that maspin correlates with better differentiated phenotypes and better survival, and that maspin induces the expression of Bax (19) and p21 WAF1/CIP1 (20), suggests that maspin may participate in specific transcriptional regulation. To this end, an earlier yeast two-hybrid screening suggests that maspin may bind to histone deacetylase 1 (HDAC1; ref.…”

Section: Introductionmentioning

confidence: 99%

Endogenous Inhibition of Histone Deacetylase 1 by Tumor-Suppressive Maspin

Li¹,

Su²,

Meng³

et al. 2006

Cancer Research

117

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Maspin, a noninhibitory serine protease inhibitor, exerts multifaceted tumor-suppressive effects. Maspin expression is associated with better differentiated phenotypes, better cancer prognosis, and better drug sensitivity. Consistently, maspin also correlates with increased expression of Bax and p21 WAF1/CIP1 . Interestingly, histone deacetylase 1 (HDAC1), a major HDAC responsible for histone deacetylation, was shown to interact with maspin in a yeast two-hybrid screening. In this study, we confirmed the maspin/HDAC1 interaction in human prostate tissues, in prostate cancer cell lines, and with purified maspin. We produced several lines of evidence that support an inhibitory effect of maspin on HDAC1 through direct molecular interaction, which was detected in both the nucleus and the cytoplasm. Both endogenously expressed maspin and purified maspin inhibited HDAC1. In contrast, small interfering RNA (siRNA) silencing of maspin in PC3 cells increased HDAC activity. Accordingly, maspin-transfected DU145 cells exhibited increased expression of HDAC1 target genes Bax, cytokeratin 18 (CK18), and p21 WAF1/CIP1 , whereas maspin siRNA decreased CK18 expression in PC3 cells. The maspin effect on HDAC1 correlated with an increased sensitivity to cytotoxic HDAC inhibitor M344. Interestingly, glutathione S-transferase (GST, another maspin partner) was detected in the maspin/HDAC1 complex. Furthermore, a COOH-terminally truncated maspin mutant, which bound to HDAC1 but not GST, did not increase histone acetylation. Although HDACs, especially the highly expressed HDAC1, are promising therapeutic targets in cancer intervention, our data raise a novel hypothesis that the endogenous inhibitory effect of maspin on HDAC1 is coupled with glutathione-based protein modification, and provide new leads toward future developments of specific HDAC1-targeting strategies. (Cancer Res 2006; 66(18): 9323-9)

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The Human Myoepithelial Cell Exerts Antiproliferative Effects on Breast Carcinoma Cells Characterized by p21WAF1/CIP1Induction, G2/M Arrest, and Apoptosis

Cited by 85 publications

References 18 publications

Maspin sensitizes breast carcinoma cells to induced apoptosis

Maspin sensitizes breast carcinoma cells to induced apoptosis

Enhanced efficiency and specificity of ovarian cancer gene therapy in rats with a novel nonviral gene delivery system (GE7) via intraovarian artery perfusion approach

Endogenous Inhibition of Histone Deacetylase 1 by Tumor-Suppressive Maspin

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