TY - JOUR
T1 - Tumor induction and tissue atrophy in mice lacking E2F-1
AU - Yamasaki, Lili
AU - Jacks, Tyler
AU - Bronson, Roderick
AU - Goillot, Evelyne
AU - Harlow, Ed
AU - Dyson, Nicholas J.
N1 - Funding Information:
We thank Kristian Helin and Andrea Talis for providing the mouse E2F-1 cDNA; Kristian Helin for anti-E2F-1 monoclonal antibodies; John Mkwandawire for technical assistance in chimaera production; and Jim Koh, Marc Vidal, Nick Heintz, and Joshua La Baer for critical reading of this manuscript. We also thank Dr. Christopher Fletcher (Brigham and Women's Hospital) for his histopathological consultation. L. Y. further thanks Marie Yamasaki, Li-Huei Tsai, Andrea Talis, and Susanne Sternthal for support throughout this project. We are grateful to the past and present members of the Laboratory of Molecular Oncology (Massachusetts General Hospital Cancer Center) and members of the Jacks laboratory for helpful discussions and advice. T. J. is an Assistant Investigator of the Howard Hughes Medical Institute, and E. H. is an American Cancer Society Scholar. This work was supported by National Institutes of Health (NIH) grants CA60636 to E. H., CA64402 to N. D., CA42063 to T. J., and an NIH postdoctoral fellowship CA60451 to L. Y.
PY - 1996/5
Y1 - 1996/5
N2 - The retinoblastoma tumor suppressor protein (pRB) is a transcriptional repressor that regulates gene expression by physically associating with transcription factors such as E2F family members. Although pRB and its upstream regulators are commonly mutated in human cancer, the physiological role of the pRB-E2F pathway is unknown. To address the function of E2F-1 and pRB/E2F-1 complexes in vivo, we have produced mice homozygous for a nonfunctional E2F-1 allele. Mice lacking E2F-1 are viable and fertile, yet experience testicular atrophy and exocrine gland dysplasia. Surprisingly, mice lacking E2F-1 develop a broad and unusual spectrum of tumors. Although overexpression of E2F-1 in tissue culture cells can stimulate cell proliferation and be oncogenic, loss of E2F-1 in mice results in tumorigenesis, demonstrating that E2F-1 also functions as a tumor suppressor.
AB - The retinoblastoma tumor suppressor protein (pRB) is a transcriptional repressor that regulates gene expression by physically associating with transcription factors such as E2F family members. Although pRB and its upstream regulators are commonly mutated in human cancer, the physiological role of the pRB-E2F pathway is unknown. To address the function of E2F-1 and pRB/E2F-1 complexes in vivo, we have produced mice homozygous for a nonfunctional E2F-1 allele. Mice lacking E2F-1 are viable and fertile, yet experience testicular atrophy and exocrine gland dysplasia. Surprisingly, mice lacking E2F-1 develop a broad and unusual spectrum of tumors. Although overexpression of E2F-1 in tissue culture cells can stimulate cell proliferation and be oncogenic, loss of E2F-1 in mice results in tumorigenesis, demonstrating that E2F-1 also functions as a tumor suppressor.
UR - http://www.scopus.com/inward/record.url?scp=0029888359&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81254-4
DO - 10.1016/S0092-8674(00)81254-4
M3 - Article
C2 - 8653789
AN - SCOPUS:0029888359
SN - 0092-8674
VL - 85
SP - 537
EP - 548
JO - Cell
JF - Cell
IS - 4
ER -