To Rb or not to Rb

Caution and more experiments are in order, say Jiang and Zacksenhaus (page 185), for drug companies hoping to activate the Rb pathway with anticancer compounds. The authors have found that expression of a constitutively active version of the tumor suppressor Rb can result in the counterintuitive outcome of more tumor formation.

Initially, expression of activated Rb in transgenicmice does suppress cell proliferation somewhat. But Jiang and Zacksenhaus suggest that this growth suppression may also positively select for cells with transforming mutations. Usually most cells with such mutations would be eliminated by apoptosis. But Rb is known to suppress apoptosis, and this appears to occur in the transgenic mice. In mammary tissue, where the tumors are eventually seen, apoptosis during involution is reduced by 44%.

This failure in apoptosis may give rise to the focal hyperplastic nodules that the...