FIG. 6.

Sustained E2F activity induces pRB-dependent senescence-like features. (A) Morphological changes as a consequence of E2F activity. Hematoxylin- and eosin-stained intermediate lobe of wild-type and transgenic mice treated for 6 months with tamoxifen. Note the increased nucleoplasmic-cytoplasmic ratio in transgenic animals compared to the wild type. (B) Accumulation of senescence markers upon sustained E2F activity. Panels show staining of either pituitary gland sections derived from wild-type (WT) and transgenic (Tg) animals or pituitary tumors derived from Rb^+/− mice. (Upper panel) Two magnifications of DAPI staining showing the formation of senescence-associated heterochromatic foci (SAHFs) in the intermediate lobe of transgenic animals upon sustained E2F activity. Note the formation of foci in transgenic animals treated for 6 months. (Lower panels) Immunohistochemistry analysis of p16^Ink4a and p19^Arf in the intermediate lobe. (C) Percentage of p16^Ink4a and senescence-associated heterochromatic focus-positive melanotrophs in the intermediate lobe of wild-type and transgenic mice treated for the indicated times with tamoxifen (TAM) and in the intermediate lobe tumor of Rb^+/− mice.