Progesterone Receptor Induces ErbB-2 Nuclear Translocation To Promote Breast Cancer Growth via a Novel Transcriptional Effect: ErbB-2 Function as a Coactivator of Stat3

被引：84

作者：

Beguelin, Wendy ^{[1
]}

Diaz Flaque, Maria Celeste ^{[1
]}

Proietti, Cecilia J. ^{[1
]}

Cayrol, Florencia ^{[1
]}

Rivas, Martin A. ^{[1
]}

Tkach, Mercedes ^{[1
]}

Rosemblit, Cinthia ^{[1
]}

Tocci, Johanna M. ^{[1
]}

Charreau, Eduardo H. ^{[1
]}

Schillaci, Roxana ^{[1
]}

Elizalde, Patricia V. ^{[1
]}

机构：

[1] Consejo Nacl Invest Cient & Tecn, IBYME, Lab Mol Mech Carcinogenesis, Buenos Aires, DF, Argentina

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2010年 / 30卷 / 23期

关键词：

CELL-PROLIFERATION; SIGNAL TRANSDUCER; CYCLIN D1; IN-VIVO; UP-REGULATION; ACTIVATION; SRC; PROTEIN; GENE; MECHANISM;

D O I：

10.1128/MCB.00012-10

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Progesterone receptor (PR) and ErbB-2 bidirectional cross talk participates in breast cancer development. Here, we identified a new mechanism of the PR and ErbB-2 interaction involving the PR induction of ErbB-2 nuclear translocation and the assembly of a transcriptional complex in which ErbB-2 acts as a coactivator of Stat3. We also highlighted that the function of ErbB-2 as a Stat3 coactivator drives progestin-induced cyclin D1 promoter activation. Notably, PR is also recruited together with Stat3 and ErbB-2 to the cyclin D1 promoter, unraveling a new and unexpected nonclassical PR genomic mechanism. The assembly of the nuclear Stat3/ErbB-2 transcriptional complex plays a key role in the proliferation of breast tumors with functional PR and ErbB-2. Our findings reveal a novel therapeutic intervention for PR-and ErbB-2-positive breast tumors via the specific blockage of ErbB-2 nuclear translocation.

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收藏

页码：5456 / 5472

页数：17

相关论文

共 37 条

[1] THE TRANSFORMING POTENTIAL OF THE C-ERBB-2 PROTEIN IS REGULATED BY ITS AUTOPHOSPHORYLATION AT THE CARBOXYL-TERMINAL DOMAIN [J].

AKIYAMA, T ;

MATSUDA, S ;

NAMBA, Y ;

SAITO, T ;

TOYOSHIMA, K ;

YAMAMOTO, T .

MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (02) :833-842

[2]

[Anonymous], 1996, GUID CAR US LAB AN

[3] Interactions between progestins and heregulin (HRG) signaling pathways:: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas [J].

Balañá, ME ;

Lupu, R ;

Labriola, L ;

Charreau, EH ;

Elizalde, PV .

ONCOGENE, 1999, 18 (46) :6370-6379

[4] Cytoplasmic transport of Stat3 by receptor-mediated endocytosis [J].

Bild, AH ;

Turkson, J ;

Jove, R .

EMBO JOURNAL, 2002, 21 (13) :3255-3263

[5] Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases [J].

Boonyaratanakornkit, V ;

Scott, MP ;

Ribon, V ;

Sherman, L ;

Anderson, SM ;

Maller, JL ;

Miller, WT ;

Edwards, DP .

MOLECULAR CELL, 2001, 8 (02) :269-280

[6] The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle [J].

Boonyaratanakornkit, Viroj ;

McGowan, Eileen ;

Sherman, Lori ;

Mancini, Michael A. ;

Cheskis, Boris J. ;

Edwards, Dean P. .

MOLECULAR ENDOCRINOLOGY, 2007, 21 (02) :359-375

[7] Stat3 as an oncogene [J].

Bromberg, JF ;

Wrzeszczynska, MH ;

Devgan, G ;

Zhao, YX ;

Pestell, RG ;

Albanese, C ;

Darnell, JE .

CELL, 1999, 98 (03) :295-303

[8] Stat3 activation is required for cellular transformation by v-src [J].

Bromberg, JF ;

Horvath, CM ;

Besser, D ;

Lathem, WW ;

Darnell, JE .

MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (05) :2553-2558

[9] Progestin effects on breast cancer cell proliferation, proteases activation, and in vivo development of metastatic phenotype all depend on progesterone receptor capacity to activate cytoplasmic signaling pathways [J].

Carnevale, Romina P. ;

Proietti, Cecilia J. ;

Salatino, Mariana ;

Urtreger, Alejandro ;

Peluffo, Guillermo ;

Edwards, Dean P. ;

Boonyaratanakornkit, Viroj ;

Charreau, Eduardo H. ;

Joffe, Elisa Bal de Kier ;

Schillaci, Roxana ;

Elizalde, Patricia V. .

MOLECULAR ENDOCRINOLOGY, 2007, 21 (06) :1335-1358

[10] ErbB-2 induces the Cyclin D1 gene in prostate epithelial cells in vitro and in vivo [J].

Casimiro, Mathew ;

Rodrignez, Olga ;

Pootrakul, Llana ;

Aventian, Maral ;

Lushina, Nadia ;

Cromelin, Caroline ;

Ferzli, Georgina ;

Johnson, Kevin ;

Fricke, Stanley ;

Diba, Fantalmn ;

Kallakury, Bhaskar ;

Ohanyerenwa, Chioma ;

Chen, Maxine ;

Ostrowski, Michael ;

Hung, Mien-Chie ;

Rabbani, Shafaat A. ;

Datar, Ram ;

Cote, Richard ;

Pestell, Richard ;

Albanese, Chris .

CANCER RESEARCH, 2007, 67 (09) :4364-4372

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