CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3.
Numerous cytogenetic and molecular studies of breast cancer have identified frequent loss of heterozygosity (LOH) of the long arm of human chromosome 16. On the basis of these data, the likely locations of breast cancer tumor suppressor genes are bands 16q22.1 and 16q24.3. We have mapped the CBFA2T3 (MTG16) gene, previously cloned as a fusion partner of the AML1 protein from a rare (16;21) leukemia translocation, to the 16q24.3 breast cancer LOH region. The expression of CBFA2T3 was significantly reduced in a number of breast cancer cell lines and in primary breast tumors, including early ductal carcinomas in situ, when compared with nontransformed breast epithelial cell lines and normal breast tissue. Reintroduction of CBFA2T3 into different breast tumor derived cell lines with decreased expression of this gene reduced colony growth on plastic and in soft agar. CBFA2T3 was shown to function as a transcriptional repressor when tethered to the GAL4 DNA-binding domain in a reporter gene assay and, therefore, has the potential to be a transcriptional repressor in normal breast epithelial cells. Taken together, these findings suggest that CBFA2T3 is a likely candidate for the breast cancer tumor suppressor gene that is the target for the frequent 16q24 LOH in breast neoplasms.
Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide 5006, South Australia, Australia. marinak@wch.bionomics.com.au
Marina
M
Kochetkova
Olivia L D
OL
McKenzie
Anthony J
AJ
Bais
Julie M
JM
Martin
Genevieve A
GA
Secker
Ram
R
Seshadri
Jason A
JA
Powell
Susan J
SJ
Hinze
Alison E
AE
Gardner
Hayley E
HE
Spendlove
Nathan J
NJ
O'Callaghan
Anne-Marie
AM
Cleton-Jansen
Cees
C
Cornelisse
Scott A
SA
Whitmore
Joanna
J
Crawford
Gabriel
G
Kremmidiotis
Grant R
GR
Sutherland
David F
DF
Callen
D001943:Breast Neoplasms / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D010750:Phosphoproteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C115744:CBFA2T3 protein, human; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins