The Requirement for Cyclin D Function in Tumor Maintenance

被引：285

作者：

Choi, Yoon Jong ^{[1
,8
]}

Li, Xiaoyu ^{[3
,9
]}

Hydbring, Per ^{[1
,8
]}

Sanda, Takaomi ^{[2
,7
,10
]}

Stefano, Joanna ^{[1
]}

Christie, Amanda L. ^{[4
]}

Signoretti, Sabina ^{[5
,6
]}

Look, A. Thomas ^{[2
,7
,10
]}

Kung, Andrew L. ^{[4
,10
]}

von Boehmer, Harald ^{[3
,9
]}

Sicinski, Piotr ^{[1
,8
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[3] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA

[4] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02215 USA

[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[6] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[7] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[9] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

来源：

CANCER CELL | 2012年 / 22卷 / 04期

基金：

日本学术振兴会;

关键词：

TRANSGENIC MICE; CELLULAR SENESCENCE; OXIDATIVE STRESS; BREAST-CANCER; IN-VIVO; TUMORIGENESIS; CELLS; GENE; ONCOGENESIS; INHIBITION;

D O I：

10.1016/j.ccr.2012.09.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

D-cyclins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment, we engineered mouse strains that allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D-associated kinase activity in mice bearing ErbB2-driven mammary carcinomas triggered tumor cell senescence, without compromising the animals' health. Ablation of cyclin D3 in mice bearing Notch 1-driven T cell acute lymphoblastic leukemias (T-ALL) triggered tumor cell apoptosis. Such selective killing of leukemic cells can also be achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Inhibition of cyclin D-kinase activity represents a highly-selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues.

引用

页码：438 / 451

页数：14

共 51 条

[31] Cyclin D as a therapeutic target in cancer [J].

Musgrove, Elizabeth A. ;

Caldon, C. Elizabeth ;

Barraclough, Jane ;

Stone, Andrew ;

Sutherland, Robert L. .

NATURE REVIEWS CANCER, 2011, 11 (08) :558-572

[32] Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence [J].

Narita, M ;

Nunez, S ;

Heard, E ;

Narita, M ;

Lin, AW ;

Hearn, SA ;

Spector, DL ;

Hannon, GJ ;

Lowe, SW .

CELL, 2003, 113 (06) :703-716

[33] FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to γ-secretase inhibitors [J].

O'Neil, Jennifer ;

Grim, Jonathan ;

Strack, Peter ;

Rao, Sudhir ;

Tibbitts, Deanne ;

Winter, Christopher ;

Hardwick, James ;

Welcker, Markus ;

Meijerink, Jules P. ;

Pieters, Rob ;

Draetta, Giulio ;

Sears, Rosalie ;

Clurman, Bruce E. ;

Look, A. Thomas .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1813-1824

[34] FoxM1, a critical regulator of oxidative stress during oncogenesis [J].

Park, Hyun Jung ;

Carr, Janai R. ;

Wang, Zebin ;

Nogueira, Veronique ;

Hay, Nissim ;

Tyner, Angela L. ;

Lau, Lester F. ;

Costa, Robert H. ;

Raychaudhuri, Pradip .

EMBO JOURNAL, 2009, 28 (19) :2908-2918

[35] A Synthetic Lethal Interaction between K-Ras Oncogenes and Cdk4 Unveils a Therapeutic Strategy for Non-small Cell Lung Carcinoma [J].

Puyol, Marta ;

Martin, Alberto ;

Dubus, Pierre ;

Mulero, Francisca ;

Pizcueta, Pilar ;

Khan, Gulfaraz ;

Guerra, Carmen ;

Santamaria, David ;

Barbacid, Mariano .

CANCER CELL, 2010, 18 (01) :63-73

[36] Cyclin-dependent kinase 4 expression is essential for neu-induced breast tumorigenesis [J].

Reddy, HKDL ;

Mettus, RV ;

Rane, SG ;

Graña, X ;

Litvin, J ;

Reddy, EP .

CANCER RESEARCH, 2005, 65 (22) :10174-10178

[37] Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo [J].

Robles, AI ;

Rodriguez-Puebla, ML ;

Glick, AB ;

Trempus, C ;

Hansen, L ;

Sicinski, P ;

Tennant, RW ;

Weinberg, RA ;

Yuspa, SH ;

Conti, CJ .

GENES & DEVELOPMENT, 1998, 12 (16) :2469-2474

[38] CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-lndependent mechanisms [J].

Ruas, Margarida ;

Gregory, Fiona ;

Jones, Rebecca ;

Poolman, Robert ;

Starborg, Maria ;

Rowe, Janice ;

Brookes, Sharon ;

Peters, Gordon .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (12) :4273-4282

[39] Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry [J].

Sage, J ;

Miller, AL ;

Pérez-Mancera, PA ;

Wysocki, JM ;

Jacks, T .

NATURE, 2003, 424 (6945) :223-228

[40] Living with or without cyclins and cyclin-dependent kinases [J].

Sherr, CJ ;

Roberts, JM .

GENES & DEVELOPMENT, 2004, 18 (22) :2699-2711

← 1 2 3 4 5 6 →