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Journal of Virology, November 2006, p. 11409-11415, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00234-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Selection of Early-Occurring Mutations Dictates Hormone-Independent Progression in Mouse Mammary Tumor Lines{triangledown}

Albana Gattelli,1,2 María N. Zimberlin,1,2 Roberto P. Meiss,2 Lucio H. Castilla,3 and Edith C. Kordon1,2*

IFIBYNE and ILEX (CONICET), Facultad de Ciencias Exactas y Naturales, UBA, (1428) Buenos Aires,1 IIHEMA and IEO, Academia Nacional de Medicina, (1425) Buenos Aires,Argentina,2 Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 016053

Received 1 February 2006/ Accepted 30 August 2006

Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.

* Corresponding author. Mailing address: IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, UBA Ciudad Universitaria, Pabellón 2, 2do piso, (1428) Buenos Aires, Argentina. Phone: 5411-4576-3300/09, ext. 483/213. Fax: 5411-4576-3321. E-mail: ekordon{at}qb.fcen.uba.ar.

{triangledown} Published ahead of print on 13 September 2006.

Journal of Virology, November 2006, p. 11409-11415, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00234-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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