A lecture taking place at the Crick.

: R-Ras2 drives cancer in the absence of oncogenic mutations

A long-standing paradigm in the oncology field is that cancer is driven by activating mutations in genes such as KRAS that lead to dysregulation of intracellular signaling pathways that finally lead to uncontrolled proliferation, resistance to apoptosis or to a blockade in terminal differentiation. Our preliminary data generated with a mouse model of overexpression of the wild type form of Rras2, a close relative to KRAS, leads to breast cancer in a short timeframe, without the need for additional intentional modifications of the mouse genome.

Breast tumors in those mice, termed R26-Rras2, quickly develop in breeding females soon after labor or during the breast-feeding period but not in nulliparous mice. These data point out to Rras2 being involved in the development of breast tumors related perhaps to the intense proliferation of mammary gland epithelium ocurring during pregnancy and/or during lactation. The phenotype of our Rosa26-Rras2 mice could thus be related to a transient increase in maternal breast cancer risk that peaks in women 5 years following delivery  and levels off 15 years postpartum.

Female and male mice that overexpress wild type Rras2 also develop an indolent B cell leukemia that is reminiscent of human B cell chronic lymphocytic leukemia (B-CLL). This could be related to the signaling function of this GTPase directly downstream of the B cell Receptor.

Hosted by: Pavel Tolar

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