Selection of early occurring mutations dictates hormone-independency progression in mouse mammary tumor lines

GATTELLI, A.; ZIMBERLIN, M.; CASTILLA, L.; KORDON, E.

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Año: 2006 vol. 80 p. 11409 - 11415

0022-538X

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 alsodetected 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.