A Genetic Screen in Drosophila for Metastatic Behavior

American Association for the Advancement of Science (AAAS) - Tập 302 Số 5648 - Trang 1227-1231 - 2003
Raymond Pagliarini1, Tian Xu1
1Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA

Tóm tắt

A genetic screen was designed in Drosophila to interrogate its genome for mutations sufficient to cause noninvasive tumors of the eye disc to invade neighboring or distant tissues. We found that cooperation between oncogenic Ras V12 expression and inactivation of any one of a number of genes affecting cell polarity leads to metastatic behavior, including basement membrane degradation, loss of E-cadherin expression, migration, invasion, and secondary tumor formation. Inactivation of these cell polarity genes cannot drive metastatic behavior alone or in combination with other tumor-initiating alterations. These findings suggest that the oncogenic background of tissues makes a distinct contribution toward metastatic development.

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Tài liệu tham khảo

10.1038/nrc865

10.1038/nrc967

10.1016/S0168-9525(99)01878-8

R. A. Pagliarini, A. T. Quinones, T. Xu, in Tumor Suppressor Genes: Regulation, Function, and Medicinal Applications, W. S. El-Deiry, Ed. (Humana, Totowa, NJ, 2003), pp. 349–381.

See supporting material on Science Online.

10.1242/dev.127.4.851

ey also expresses in the CNS ocelli and Bolwig's organ. In larvae however eyFLP did not produce visible clones outside of the noted locations.

10.1038/5965

10.1242/dev.125.1.1

10.1101/gad.947701

10.1242/dev.121.4.1053

Three phenotypic classes were observed when Ras V12 -expressing cells in mosaic flies were also made homozygous foradditional second-site mutations (862 mutant lines): reduced tumor growth (76 lines) enhanced tumor growth (9 lines) and tumors with metastatic behavior (2 lines).

10.1038/35001108

10.1126/science.289.5476.113

10.1038/nrc745

10.1073/pnas.261408198

When using the GFP-labeled collagen IV protein trap mutant cells were marked with UAS-lacZ instead of UAS-GFP .

10.1038/32433

10.1101/gad.10.6.659

10.1101/gad.10.6.672

10.1006/dbio.2000.9671

10.1083/jcb.134.1.149

10.1038/ncb897

10.1038/ncb896

10.1016/S0092-8674(00)81765-1

10.1016/S0092-8674(00)80679-0

10.1002/j.1460-2075.1996.tb00738.x

10.1242/dev.120.8.2121

10.1016/S0092-8674(00)81512-3

10.1038/70293

10.1038/nrc822

10.1016/S1357-4310(99)01461-6

10.1038/418823a

10.1242/dev.117.4.1223

10.1016/S0896-6273(00)80701-1

10.1242/dev.124.4.761

10.1242/dev.118.2.401

10.1016/S0092-8674(00)81766-3

We thank D. DiMaio A. Horwich R. Lifton D. Stern and K. White for critical review; R. Li T. Ni and H. Lee for participating in the screen; X. Fei for transgene injections; E. Hersperger and A. Shearn for teaching transplantation techniques; and D. Bilder M. Birnbaum H. Chang L. Cooley R. Fehon P. Gallant I. Hariharan B. Hay X. Morin H. Oda J. P. Vincent and T. Uemura for strains and reagents. Supported by NIH grant CA69408 (T.X.) and the Linda Tallen and David Paul Kane Educational and Research Foundation. T.X. is a HHMI Investigator; R.A.P. is a predoctoral fellow in the Department of Genetics.

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American Association for the Advancement of Science (AAAS)

Tập 302 Số 5648

1227-1231

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