Skip to main content
Erschienen in: Breast Cancer Research and Treatment 1/2010

01.11.2010 | Preclinical study

The G12 family proteins upregulate matrix metalloproteinase-2 via p53 leading to human breast cell invasion

verfasst von: Eun-Sook Kim, Jae-Boon Jeong, Seonhoe Kim, Kyung-Min Lee, Eunyoung Ko, Dong-Young Noh, Ki-Tae Hwang, Ji Hee Ha, Chang Ho Lee, Sang Geon Kim, Aree Moon

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2010

Einloggen, um Zugang zu erhalten

Abstract

Although mounting evidence suggests a role for G12 proteins, Gα12 and Gα13, in tumor progression, a direct role of G12 proteins has not been determined. This study aims to elucidate the molecular mechanism for a tumorigenic and invasive potential of Gα12 and Gα13 in MCF10A human breast epithelial cells. Here, we report, for the first time, that Gα12 and Gα13 induce upregulation of matrix metalloproteinase (MMP)-2 leading to the invasive and migratory phenotypes in MCF10A cells. We further show that p53 is an important transcription factor for induction of MMP-2 transcriptional activation by Gα12/13. Gα12/13-induced MMP-2 upregulation, invasion, and migration are dependent on the activation of Ras, Rac1, MKK3/6, p38, and Akt. Using human breast tissue samples, we demonstrate that the expression levels of Gα12 and MMP-2 are strongly correlated with the pathogenically diagnosed cancer (P < 0.0001). Moreover, the expression of Gα12 shows a strong correlation with that of MMP-2 in human breast cancer tissues, implicating the in vivo tumorigenic potential of Gα12. Taken together, this study elucidated the role of G12 proteins in regulating processes for MMP-2 expression and malignant phenotypic conversion of MCF10A human breast epithelial cells, providing a molecular basis for the promoting role of Gα12 and Gα13 in breast cell invasion.
Literatur
1.
Zurück zum Zitat Dhanasekaran N, Dermott JM (1996) Signaling by the G12 class of G proteins. Cell Signal 8:235–245CrossRefPubMed Dhanasekaran N, Dermott JM (1996) Signaling by the G12 class of G proteins. Cell Signal 8:235–245CrossRefPubMed
2.
Zurück zum Zitat Yoshioka K, Matsumura F, Akedo H, Itoh K (1998) Small GTP-binding protein Rho stimulates the actomyosin system, leading to invasion of tumor cells. J Biol Chem 273:5146–5154CrossRefPubMed Yoshioka K, Matsumura F, Akedo H, Itoh K (1998) Small GTP-binding protein Rho stimulates the actomyosin system, leading to invasion of tumor cells. J Biol Chem 273:5146–5154CrossRefPubMed
3.
Zurück zum Zitat Huang C, Hujer KM, Wu Z, Miller RT (2004) The Ca2 + -sensing receptor couples to Galpha12/13 to activate phospholipase D in Madin-Darby canine kidney cells. Am J Physiol Cell Physiol 286:C22–C30CrossRefPubMed Huang C, Hujer KM, Wu Z, Miller RT (2004) The Ca2 + -sensing receptor couples to Galpha12/13 to activate phospholipase D in Madin-Darby canine kidney cells. Am J Physiol Cell Physiol 286:C22–C30CrossRefPubMed
4.
Zurück zum Zitat Rumenapp U, Asmus M, Schablowski H, Woznicki M, Han L, Jakobs KH, Fahimi-Vahid M, Michalek C, Wieland T, Schmidt M (2001) The M3 muscarinic acetylcholine receptor expressed in HEK-293 cells signals to phospholipase D via G12 but not Gq-type G proteins: regulators of G proteins as tools to dissect pertussis toxin-resistant G proteins in receptor-effector coupling. J Biol Chem 276:2474–2479CrossRefPubMed Rumenapp U, Asmus M, Schablowski H, Woznicki M, Han L, Jakobs KH, Fahimi-Vahid M, Michalek C, Wieland T, Schmidt M (2001) The M3 muscarinic acetylcholine receptor expressed in HEK-293 cells signals to phospholipase D via G12 but not Gq-type G proteins: regulators of G proteins as tools to dissect pertussis toxin-resistant G proteins in receptor-effector coupling. J Biol Chem 276:2474–2479CrossRefPubMed
5.
Zurück zum Zitat Shepard LW, Yang M, Xie P, Browning DD, Voyno-Yasenetskaya T, Kozasa T, Ye RD (2001) Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by the G protein-coupled receptor of Kaposi’s sarcoma-associated herpesvirus involve G alpha(13) and RhoA. J Biol Chem 276:45979–45987CrossRefPubMed Shepard LW, Yang M, Xie P, Browning DD, Voyno-Yasenetskaya T, Kozasa T, Ye RD (2001) Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by the G protein-coupled receptor of Kaposi’s sarcoma-associated herpesvirus involve G alpha(13) and RhoA. J Biol Chem 276:45979–45987CrossRefPubMed
6.
Zurück zum Zitat Fukuhara S, Marinissen MJ, Chiariello M, Gutkind JS (2000) Signaling from G protein-coupled receptors to ERK5/Big MAPK 1 involves Galpha q and Galpha 12/13 families of heterotrimeric G proteins. Evidence for the existence of a novel Ras AND Rho-independent pathway. J Biol Chem 275:21730–21736CrossRefPubMed Fukuhara S, Marinissen MJ, Chiariello M, Gutkind JS (2000) Signaling from G protein-coupled receptors to ERK5/Big MAPK 1 involves Galpha q and Galpha 12/13 families of heterotrimeric G proteins. Evidence for the existence of a novel Ras AND Rho-independent pathway. J Biol Chem 275:21730–21736CrossRefPubMed
7.
Zurück zum Zitat Nishida M, Tanabe S, Maruyama Y, Mangmool S, Urayama K, Nagamatsu Y, Takagahara S, Turner JH, Kozasa T, Kobayashi H, Sato Y, Kawanishi T, Inoue R, Nagao T, Kurose H (2005) G alpha 12/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes. J Biol Chem 280:18434–18441CrossRefPubMed Nishida M, Tanabe S, Maruyama Y, Mangmool S, Urayama K, Nagamatsu Y, Takagahara S, Turner JH, Kozasa T, Kobayashi H, Sato Y, Kawanishi T, Inoue R, Nagao T, Kurose H (2005) G alpha 12/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes. J Biol Chem 280:18434–18441CrossRefPubMed
8.
Zurück zum Zitat Mitsui H, Takuwa N, Kurokawa K, Exton JH, Takuwa Y (1997) Dependence of activated Galpha12-induced G1 to S phase cell cycle progression on both Ras/mitogen-activated protein kinase and Ras/Rac1/Jun N-terminal kinase cascades in NIH3T3 fibroblasts. J Biol Chem 272:4904–4910CrossRefPubMed Mitsui H, Takuwa N, Kurokawa K, Exton JH, Takuwa Y (1997) Dependence of activated Galpha12-induced G1 to S phase cell cycle progression on both Ras/mitogen-activated protein kinase and Ras/Rac1/Jun N-terminal kinase cascades in NIH3T3 fibroblasts. J Biol Chem 272:4904–4910CrossRefPubMed
9.
Zurück zum Zitat Xu N, Bradley L, Ambdukar I, Gutkind JS (1993) A mutant alpha subunit of G12 potentiates the eicosanoid pathway and is highly oncogenic in NIH 3T3 cells. Proc Natl Acad Sci USA 90:6741–6745CrossRefPubMed Xu N, Bradley L, Ambdukar I, Gutkind JS (1993) A mutant alpha subunit of G12 potentiates the eicosanoid pathway and is highly oncogenic in NIH 3T3 cells. Proc Natl Acad Sci USA 90:6741–6745CrossRefPubMed
10.
Zurück zum Zitat Vara Prasad MV, Shore SK, Dhanasekaran N (1994) Activated mutant of G alpha 13 induces Egr-1, c-fos, and transformation in NIH 3T3 cells. Oncogene 9:2425–2429PubMed Vara Prasad MV, Shore SK, Dhanasekaran N (1994) Activated mutant of G alpha 13 induces Egr-1, c-fos, and transformation in NIH 3T3 cells. Oncogene 9:2425–2429PubMed
11.
Zurück zum Zitat Meigs TE, Fields TA, McKee DD, Casey PJ (2001) Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta -catenin release. Proc Natl Acad Sci USA 98:519–524CrossRefPubMed Meigs TE, Fields TA, McKee DD, Casey PJ (2001) Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta -catenin release. Proc Natl Acad Sci USA 98:519–524CrossRefPubMed
12.
Zurück zum Zitat Kelly P, Casey PJ, Meigs TE (2007) Biologic functions of the G12 subfamily of heterotrimeric g proteins: growth, migration, and metastasis. Biochemistry 46:6677–6687CrossRefPubMed Kelly P, Casey PJ, Meigs TE (2007) Biologic functions of the G12 subfamily of heterotrimeric g proteins: growth, migration, and metastasis. Biochemistry 46:6677–6687CrossRefPubMed
13.
Zurück zum Zitat Bian D, Mahanivong C, Yu J, Frisch SM, Pan ZK, Ye RD, Huang S (2006) The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migration. Oncogene 25:2234–2244CrossRefPubMed Bian D, Mahanivong C, Yu J, Frisch SM, Pan ZK, Ye RD, Huang S (2006) The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migration. Oncogene 25:2234–2244CrossRefPubMed
14.
Zurück zum Zitat Kelly P, Stemmle LN, Madden JF, Fields TA, Daaka Y, Casey PJ (2006) A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem 281:26483–26490CrossRefPubMed Kelly P, Stemmle LN, Madden JF, Fields TA, Daaka Y, Casey PJ (2006) A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem 281:26483–26490CrossRefPubMed
15.
Zurück zum Zitat Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA, Casey PJ (2006) The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci USA 103:8173–8178CrossRefPubMed Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA, Casey PJ (2006) The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci USA 103:8173–8178CrossRefPubMed
16.
Zurück zum Zitat Stetler-Stevenson WG (1999) Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 103:1237–1241CrossRefPubMed Stetler-Stevenson WG (1999) Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 103:1237–1241CrossRefPubMed
17.
Zurück zum Zitat Moon A, Kim MS, Kim TG, Kim SH, Kim HE, Chen YQ, Kim HR (2000) H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells: a role for MMP-2 in the H-ras-induced invasive phenotype. Int J Cancer 85:176–181PubMed Moon A, Kim MS, Kim TG, Kim SH, Kim HE, Chen YQ, Kim HR (2000) H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells: a role for MMP-2 in the H-ras-induced invasive phenotype. Int J Cancer 85:176–181PubMed
18.
Zurück zum Zitat Kim MS, Lee EJ, Kim HR, Moon A (2003) p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res 63:5454–5461PubMed Kim MS, Lee EJ, Kim HR, Moon A (2003) p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res 63:5454–5461PubMed
19.
Zurück zum Zitat Qin H, Sun Y, Benveniste EN (1999) The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 274:29130–29137CrossRefPubMed Qin H, Sun Y, Benveniste EN (1999) The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 274:29130–29137CrossRefPubMed
20.
Zurück zum Zitat Bian J, Sun Y (1997) Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. Mol Cell Biol 17:6330–6338PubMed Bian J, Sun Y (1997) Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. Mol Cell Biol 17:6330–6338PubMed
21.
Zurück zum Zitat Bergman MR, Cheng S, Honbo N, Piacentini L, Karliner JS, Lovett DH (2003) A functional activating protein 1 (AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through interactions with JunB-Fra1 and JunB-FosB heterodimers. Biochem J 369:485–496CrossRefPubMed Bergman MR, Cheng S, Honbo N, Piacentini L, Karliner JS, Lovett DH (2003) A functional activating protein 1 (AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through interactions with JunB-Fra1 and JunB-FosB heterodimers. Biochem J 369:485–496CrossRefPubMed
22.
Zurück zum Zitat Song H, Ki SH, Kim SG, Moon A (2006) Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res 66:10487–10496CrossRefPubMed Song H, Ki SH, Kim SG, Moon A (2006) Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res 66:10487–10496CrossRefPubMed
23.
Zurück zum Zitat Soule HD, Maloney TM, Wolman SR, Peterson WD Jr, Brenz R, McGrath CM, Russo J, Pauley RJ, Jones RF, Brooks SC (1990) Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 50:6075–6086PubMed Soule HD, Maloney TM, Wolman SR, Peterson WD Jr, Brenz R, McGrath CM, Russo J, Pauley RJ, Jones RF, Brooks SC (1990) Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 50:6075–6086PubMed
24.
Zurück zum Zitat Abdellatif M, MacLellan WR, Schneider MD (1994) p21 Ras as a governor of global gene expression. J Biol Chem 69:15423–15426 Abdellatif M, MacLellan WR, Schneider MD (1994) p21 Ras as a governor of global gene expression. J Biol Chem 69:15423–15426
25.
Zurück zum Zitat Han SI, Oh SY, Woo SH, Kim KH, Kim JH, Kim HD, Kang HS (2001) Implication of a small GTPase Rac1 in the activation of c-Jun N-terminal kinase and heat shock factor in response to heat shock. J Biol Chem 276:1889–1895CrossRefPubMed Han SI, Oh SY, Woo SH, Kim KH, Kim JH, Kim HD, Kang HS (2001) Implication of a small GTPase Rac1 in the activation of c-Jun N-terminal kinase and heat shock factor in response to heat shock. J Biol Chem 276:1889–1895CrossRefPubMed
26.
Zurück zum Zitat Ma Z, Qin H, Benveniste EN (2001) Transcriptional suppression of matrix metalloproteinase-9 gene expression by IFN-gamma and IFN-beta: critical role of STAT-1alpha. J Immunol 167:5150–5159PubMed Ma Z, Qin H, Benveniste EN (2001) Transcriptional suppression of matrix metalloproteinase-9 gene expression by IFN-gamma and IFN-beta: critical role of STAT-1alpha. J Immunol 167:5150–5159PubMed
27.
Zurück zum Zitat Kim MS, Lee SM, Kim WD, Ki SH, Moon A, Lee CH, Kim SG (2007) G alpha 12/13 basally regulates p53 through Mdm4 expression. Mol Cancer Res 5:473–484CrossRefPubMed Kim MS, Lee SM, Kim WD, Ki SH, Moon A, Lee CH, Kim SG (2007) G alpha 12/13 basally regulates p53 through Mdm4 expression. Mol Cancer Res 5:473–484CrossRefPubMed
28.
Zurück zum Zitat Sabeh F, Ota I, Holmbeck K, Birkedal-Hansen H, Soloway P, Balbin M, Lopez-Otin C, Shapiro S, Inada M, Krane S, Allen E, Chung D, Weiss SJ (2004) Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP. J Cell Biol 167:769–781CrossRefPubMed Sabeh F, Ota I, Holmbeck K, Birkedal-Hansen H, Soloway P, Balbin M, Lopez-Otin C, Shapiro S, Inada M, Krane S, Allen E, Chung D, Weiss SJ (2004) Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP. J Cell Biol 167:769–781CrossRefPubMed
29.
Zurück zum Zitat Ki SH, Cho IJ, Choi DW, Kim SG (2005) Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression. Mol Cell Biol 25:4150–4165CrossRefPubMed Ki SH, Cho IJ, Choi DW, Kim SG (2005) Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression. Mol Cell Biol 25:4150–4165CrossRefPubMed
30.
Zurück zum Zitat Moon A, Yong H-Y, Song J-I, Cukovic D, Salagrama S, Kaplan D, Putt D, Kim H, Dombkowski A, Kim HR (2008) Global gene expression profiling unveils S100A8/A9 as candidate markers in H-ras-mediated human breast epithelial cell invasion. Mol Cancer Res 6:1544–1553CrossRefPubMed Moon A, Yong H-Y, Song J-I, Cukovic D, Salagrama S, Kaplan D, Putt D, Kim H, Dombkowski A, Kim HR (2008) Global gene expression profiling unveils S100A8/A9 as candidate markers in H-ras-mediated human breast epithelial cell invasion. Mol Cancer Res 6:1544–1553CrossRefPubMed
31.
Zurück zum Zitat Kaunas R, Nguyen P, Usami S, Chien S (2005) Cooperative effects of Rho and mechanical stretch on stress fiber organization. PNAS 102:15895–15900CrossRefPubMed Kaunas R, Nguyen P, Usami S, Chien S (2005) Cooperative effects of Rho and mechanical stretch on stress fiber organization. PNAS 102:15895–15900CrossRefPubMed
32.
Zurück zum Zitat Braga VM, Machesky LM, Hall A, Hotchin NA (1997) The Small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell–cell contacts. J Cell Biol 137:1421–1431CrossRefPubMed Braga VM, Machesky LM, Hall A, Hotchin NA (1997) The Small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell–cell contacts. J Cell Biol 137:1421–1431CrossRefPubMed
33.
Zurück zum Zitat Nobes CD, Hall A (1999) Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol 144:1235–1244CrossRefPubMed Nobes CD, Hall A (1999) Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol 144:1235–1244CrossRefPubMed
34.
Zurück zum Zitat Munoz-Najar UM, Neurath KM, Vumbaca F, Claffey KP (2006) Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation. Oncogene 25:2379–2392CrossRefPubMed Munoz-Najar UM, Neurath KM, Vumbaca F, Claffey KP (2006) Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation. Oncogene 25:2379–2392CrossRefPubMed
35.
Zurück zum Zitat Ghosh K, Thodeti CK, Dudley AC, Mammoto A, Klagsbrun M, Ingber DE (2008) Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro. PNAS 105:11305–11310CrossRefPubMed Ghosh K, Thodeti CK, Dudley AC, Mammoto A, Klagsbrun M, Ingber DE (2008) Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro. PNAS 105:11305–11310CrossRefPubMed
36.
Zurück zum Zitat Goncharova EA, Goncharov DA, Lim PN, Noonan D, Krymskaya VP (2006) Modulation of cell migration and invasiveness by tumor suppressor TSC2 in lymphangioleiomyomatosis. Am J Respir Cell Mol Biol 34:473–480CrossRefPubMed Goncharova EA, Goncharov DA, Lim PN, Noonan D, Krymskaya VP (2006) Modulation of cell migration and invasiveness by tumor suppressor TSC2 in lymphangioleiomyomatosis. Am J Respir Cell Mol Biol 34:473–480CrossRefPubMed
37.
Zurück zum Zitat Shin I, Kim S, Song H, Kim HR, Moon A (2005) H-Ras-specific activation of Rac-MKK3/6–p38 pathway: its critical role in invasion and migration of breast epithelial cells. J Biol Chem 280:14675–14683CrossRefPubMed Shin I, Kim S, Song H, Kim HR, Moon A (2005) H-Ras-specific activation of Rac-MKK3/6–p38 pathway: its critical role in invasion and migration of breast epithelial cells. J Biol Chem 280:14675–14683CrossRefPubMed
38.
Zurück zum Zitat Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66CrossRefPubMed Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66CrossRefPubMed
39.
Zurück zum Zitat Lepley D, Paik JH, Hla T, Ferrer F (2005) The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration. Cancer Res 5:3788–3795CrossRef Lepley D, Paik JH, Hla T, Ferrer F (2005) The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration. Cancer Res 5:3788–3795CrossRef
40.
Zurück zum Zitat Chapman HA (1997) Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration. Curr Opin Cell Biol 9:714–724CrossRefPubMed Chapman HA (1997) Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration. Curr Opin Cell Biol 9:714–724CrossRefPubMed
41.
Zurück zum Zitat Chirco R, Liu XW, Jung KK, Kim HR (2006) Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev 25:99–113CrossRefPubMed Chirco R, Liu XW, Jung KK, Kim HR (2006) Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev 25:99–113CrossRefPubMed
42.
Zurück zum Zitat Haffner R, Oren M (1995) Biochemical properties and biological effects of p53. Curr Opin Genet Dev 5:84–90CrossRefPubMed Haffner R, Oren M (1995) Biochemical properties and biological effects of p53. Curr Opin Genet Dev 5:84–90CrossRefPubMed
43.
Zurück zum Zitat Ko LJ, Prives C (1997) p53: puzzle and paradigm. Genes Dev 10:1054–1072CrossRef Ko LJ, Prives C (1997) p53: puzzle and paradigm. Genes Dev 10:1054–1072CrossRef
44.
Zurück zum Zitat Wadsworth SJ, Gebauer G, van Rossum GD, Dhanasekaran N (1997) Ras-dependent signaling by the GTPase-deficient mutant of Galpha12. J Biol Chem 272:28829–28832CrossRefPubMed Wadsworth SJ, Gebauer G, van Rossum GD, Dhanasekaran N (1997) Ras-dependent signaling by the GTPase-deficient mutant of Galpha12. J Biol Chem 272:28829–28832CrossRefPubMed
45.
Zurück zum Zitat Collins LR, Minden A, Karin M, Brown JH (1996) Galpha12 stimulates c-Jun NH2-terminal kinase through the small G proteins Ras and Rac. J Biol Chem 271:17349–17353CrossRefPubMed Collins LR, Minden A, Karin M, Brown JH (1996) Galpha12 stimulates c-Jun NH2-terminal kinase through the small G proteins Ras and Rac. J Biol Chem 271:17349–17353CrossRefPubMed
46.
Zurück zum Zitat Dermott JM, Ha JH, Lee CH, Dhanasekaran N (2004) Differential regulation of Jun N-terminal kinase and p38MAP kinase by Galpha12. Oncogene 23:226–232CrossRefPubMed Dermott JM, Ha JH, Lee CH, Dhanasekaran N (2004) Differential regulation of Jun N-terminal kinase and p38MAP kinase by Galpha12. Oncogene 23:226–232CrossRefPubMed
47.
Zurück zum Zitat Nagao M, Kaziro Y, Itoh H (1999) The Src family tyrosine kinase is involved in Rho-dependent activation of c-Jun N-terminal kinase by Galpha12. Oncogene 18:4425–4434CrossRefPubMed Nagao M, Kaziro Y, Itoh H (1999) The Src family tyrosine kinase is involved in Rho-dependent activation of c-Jun N-terminal kinase by Galpha12. Oncogene 18:4425–4434CrossRefPubMed
48.
Zurück zum Zitat Jho EH, Davis RJ, Malbon CC (1997) c-Jun amino-terminal kinase is regulated by Ga12/Ga13 and obligate for differentiation of P19 embryonal carcinoma cells by retinoic acid. J Biol Chem 272:24468–24474CrossRefPubMed Jho EH, Davis RJ, Malbon CC (1997) c-Jun amino-terminal kinase is regulated by Ga12/Ga13 and obligate for differentiation of P19 embryonal carcinoma cells by retinoic acid. J Biol Chem 272:24468–24474CrossRefPubMed
49.
Zurück zum Zitat Kurose H (2003) Ga12 and Ga13 as key regulatory mediator in signal transduction. Life Sci 74:155–161CrossRefPubMed Kurose H (2003) Ga12 and Ga13 as key regulatory mediator in signal transduction. Life Sci 74:155–161CrossRefPubMed
50.
Zurück zum Zitat Berestetskaya YV, Faure MP, Ichijo H, Voyno-Yasenetskaya TA (1998) Regulation of apoptosis by α-subunits of G12 and G13 proteins via apoptosis signal-regulating kinase-1. J Biol Chem 273:27816–27823CrossRefPubMed Berestetskaya YV, Faure MP, Ichijo H, Voyno-Yasenetskaya TA (1998) Regulation of apoptosis by α-subunits of G12 and G13 proteins via apoptosis signal-regulating kinase-1. J Biol Chem 273:27816–27823CrossRefPubMed
51.
Zurück zum Zitat Berestetskaya YV, Faure MP, Ichijo H, Voyno-Yasenetskaya TA (2001) Interaction between the Gα subunit of heterotrimeric G12 protein and Hsp90 is required for Gα12 signaling. J Biol Chem 276:46088–46093CrossRef Berestetskaya YV, Faure MP, Ichijo H, Voyno-Yasenetskaya TA (2001) Interaction between the Gα subunit of heterotrimeric G12 protein and Hsp90 is required for Gα12 signaling. J Biol Chem 276:46088–46093CrossRef
Metadaten
Titel
The G12 family proteins upregulate matrix metalloproteinase-2 via p53 leading to human breast cell invasion
verfasst von
Eun-Sook Kim
Jae-Boon Jeong
Seonhoe Kim
Kyung-Min Lee
Eunyoung Ko
Dong-Young Noh
Ki-Tae Hwang
Ji Hee Ha
Chang Ho Lee
Sang Geon Kim
Aree Moon
Publikationsdatum
01.11.2010
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2010
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0697-2

Weitere Artikel der Ausgabe 1/2010

Breast Cancer Research and Treatment 1/2010 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.