TUMOR-INDUCTION AND TISSUE ATROPHY IN MICE LACKING E2F-1

The retinoblastoma tumor suppressor protein (pRB) is a transcriptional repressor that regulates gene expression by physically associating wi th transcription factors such as E2F family members. Although pRB and its upstream regulators are commonly mutated in human cancer, the phys iological role of the pRB-E2F pathway is unknown. To address the funct ion of E2F-1 and pRB/E2F-1 complexes in vivo, we have produced mice ho mozygous for a nonfunctional E2F-1 allele. Mice lacking E2F-1 are viab le and fertile, yet experience testicular atrophy and exocrine gland d ysplasia. Surprisingly, mice lacking E2F-1 develop a broad and unusual spectrum of tumors. Although overexpression of E2F-1 in tissue cultur e cells can stimulate cell proliferation and be oncogenic, loss of E2F -1 in mice results in tumorigenesis, demonstrating that E2F-1 also fun ctions as a tumor suppressor.