TY - JOUR
T1 - Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line
AU - Saito, Midori
AU - Helin, Kristian
AU - Valentine, Marcus B.
AU - Griffith, Barbara B.
AU - Willman, Cheryl L.
AU - Harlow, Ed
AU - Look, A. Thomas
N1 - Funding Information:
We thank Susana Raimondi for cytogenetic analysis of leukemia cells, and John Gilbert for editorial review. Supported in part by Grants CA 42804, CA 20180, CA 32102, and Cancer Center Support (CORE) Grant CA-21765 from the National Cancer Institute, NIH, and by the American Lebanese Syrian Associated Charities (AL-SAC), St. Jude Children’s Research Hospital. K.H. is a fellow of the Danish Medical Research Council, and E.H. is an American Cancer Society Research Professor.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - The E2F transcription factor plays an important regulatory role in cell proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synthesize DNA. To investigate the possible involvement of E2F in hematopoietic malignancies, we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 2011, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22 chromosomal locations previously assigned E2F2 and E2F3, two additional members of the E2F family. Although deletions or structural rearrangements of E2F1 were not detected in 14 primary acute leukemia or myelodysplasia samples with structural abnormalities of chromosome 20q11, the gene was amplified and overexpressed in HEL erythroleukemia cells and translocated to other chromosomes in several established human leukemia cell lines. This study provides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexpression in erythroid progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb.
AB - The E2F transcription factor plays an important regulatory role in cell proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synthesize DNA. To investigate the possible involvement of E2F in hematopoietic malignancies, we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 2011, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22 chromosomal locations previously assigned E2F2 and E2F3, two additional members of the E2F family. Although deletions or structural rearrangements of E2F1 were not detected in 14 primary acute leukemia or myelodysplasia samples with structural abnormalities of chromosome 20q11, the gene was amplified and overexpressed in HEL erythroleukemia cells and translocated to other chromosomes in several established human leukemia cell lines. This study provides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexpression in erythroid progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb.
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U2 - 10.1016/0888-7543(95)80118-6
DO - 10.1016/0888-7543(95)80118-6
M3 - Article
C2 - 7774910
AN - SCOPUS:0028909272
SN - 0888-7543
VL - 25
SP - 130
EP - 138
JO - Genomics
JF - Genomics
IS - 1
ER -