The HMG-I oncogene causes highly penetrant, aggressive lymphoid malignancy in transgenic mice and is overexpressed in human leukemia.
HMG-I/Y is overexpressed in human cancer, although a direct role for this gene in transformation has not been established. We generated transgenic mice with HMG-I targeted to lymphoid cells. All seven informative founder HMG-I mice developed aggressive lymphoma by a mean age of 4.8 months. Tumors express T-cell markers and are transplantable. We also demonstrate that HMG-I mRNA and protein are increased in human acute lymphocytic leukemia samples. Our results show that HMG-I functions as an oncogene and suggest that it contributes to the pathogenesis of leukemia and other cancers with increased HMG-I expression.
Xu
Yi
Y
Hematology Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Sumter
Takita Felder
TF
Bhattacharya
Raka
R
Tesfaye
Abeba
A
Fuchs
Ephraim J
EJ
Wood
Lisa J
LJ
Huso
David L
DL
Resar
Linda M S
LM
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019076:Transgenes
D024243:HMGB1 Protein; D012333:RNA, Messenger