A conditional mouse model of synovial sarcoma: Insights into a myogenic origin

被引：238

作者：

Haldar, Malay

Hancock, Jeffrey D.

Coffin, Cheryl M.

Lessnick, Stephen L.

Capecchi, Mario R. ^{[1
]}

机构：

[1] Univ Utah, Dept Human Genet, Sch Med, Salt Lake City, UT 84112 USA

[2] Univ Utah, Div Pediat Hematol Oncol, Sch Med, Salt Lake City, UT 84112 USA

[3] Univ Utah, Ctr Children, Huntsman Canc Inst, Sch Med, Salt Lake City, UT 84112 USA

[4] Univ Utah, Dept Pathol, Sch Med, Salt Lake City, UT 84112 USA

[5] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Sch Med, Salt Lake City, UT 84112 USA

[6] Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA

来源：

CANCER CELL | 2007年 / 11卷 / 04期

关键词：

D O I：

10.1016/j.ccr.2007.01.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Synovial sarcoma is an aggressive soft-tissue malignancy marked by a unique t(X;l 8) translocation leading to expression of a chimeric SYT-SSX fusion protein. We report here a mouse model of synovial sarcoma based on conditional expression of the human SYT-SSX2. Using this model, we have identified myoblasts as a potential source of synovial sarcoma. Remarkably, within the skeletal muscle lineage, while expression of the oncoprotein in immature myoblasts leads to induction of synovial sarcoma with 100% penetrance, its expression in more differentiated cells induces myopathy without tumor induction. We also show that early widespread expression of the fusion protein disrupts normal embryogenesis, causing lethality.

引用

收藏

页码：375 / 388

页数：14

相关论文

共 54 条

[1] Gene expression profiling of human sarcomas: Insights into sarcoma biology [J].

Baird, K ;

Davis, S ;

Antonescu, CR ;

Harper, UL ;

Walker, RL ;

Chen, YD ;

Glatfelter, AA ;

Duray, PH ;

Meltzer, PS .

CANCER RESEARCH, 2005, 65 (20) :9226-9235

[2] Myogenic regulatory factors:: Redundant or specific functions?: Lessons from Xenopus [J].

Chanoine, C ;

Della Gaspera, B ;

Charbonnier, F .

DEVELOPMENTAL DYNAMICS, 2004, 231 (04) :662-670

[3]

CLARKE KF, 1994, J INST WATER ENV MAN, V8, P1

[4] FUSION OF SYT TO 2 GENES, SSX1 AND SSX2, ENCODING PROTEINS WITH HOMOLOGY TO THE KRUPPEL-ASSOCIATED BOX IN HUMAN SYNOVIAL SARCOMA [J].

CREW, AJ ;

CLARK, J ;

FISHER, C ;

GILL, S ;

GRIMER, R ;

MITCHELL, P ;

CHAND, A ;

SHIPLEY, J ;

GUSTERSON, BA ;

COOPER, CS .

EMBO JOURNAL, 1995, 14 (10) :2333-2340

[5] Mapping and characterization of the mouse and human SS18 genes, two human SS18-like genes and a mouse Ss18 pseudogene [J].

de Bruijn, DRH ;

Kater-Baats, E ;

Eleveld, M ;

Merkx, G ;

van Kessel, AG .

CYTOGENETICS AND CELL GENETICS, 2001, 92 (3-4) :310-319

[6]

deBruijn DRH, 1996, ONCOGENE, V13, P643

[7] IDENTIFICATION OF 2 ALTERNATIVE FUSION GENES, SYT-SSX1 AND SYT-SSX2, IN T(X-18)(P11.2-Q11.2)-POSITIVE SYNOVIAL SARCOMAS [J].

DELEEUW, B ;

BALEMANS, M ;

WEGHUIS, DO ;

VANKESSEL, AG .

HUMAN MOLECULAR GENETICS, 1995, 4 (06) :1097-1099

[8] DISTINCT XP11.2 BREAKPOINT REGIONS IN SYNOVIAL SARCOMA REVEALED BY METAPHASE AND INTERPHASE FISH - RELATIONSHIP TO HISTOLOGIC SUBTYPES [J].

DELEEUW, B ;

SUIJKERBUIJK, RF ;

WEGHUIS, DO ;

MELONI, AM ;

STENMAN, G ;

KINDBLOM, LG ;

BALEMANS, M ;

VANDENBERG, E ;

MOLENAAR, WM ;

SANDBERG, AA ;

VANKESSEL, AG .

CANCER GENETICS AND CYTOGENETICS, 1994, 73 (02) :89-94

[9] Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on RNA interference of vascular endothelial cell growth factor A [J].

Detwiller, KY ;

Fernando, NT ;

Segal, NH ;

Ryeom, SW ;

D'Amore, PA ;

Yoon, SS .

CANCER RESEARCH, 2005, 65 (13) :5881-5889

[10] Delineation of the protein domains responsible for SYT, SSX, and SYT-SSX nuclear localization [J].

dos Santos, NR ;

de Bruijn, DRH ;

Kater-Baats, E ;

Otte, AP ;

van Kessel, AG .

EXPERIMENTAL CELL RESEARCH, 2000, 256 (01) :192-202

← 1 2 3 4 5 6 →