Scaffold Attachment Factor B1 (SAFB1) heterozygosity does not influence Wnt-1 or DMBA-induced tumorigenesis.
BACKGROUND
Scaffold Attachment Factor B1 (SAFB1) is a multifunctional protein which has been implicated in breast cancer previously. We recently generated SAFB1 knockout mice (SAFB1-/-), but pleiotropic phenotypes including high lethality, dwarfism associated with low IGF-I levels, and infertility and subfertility in male and female mice, respectively, do not allow for straightforward tumorigenesis studies in these mice. Therefore, we asked whether SAFB1 heterozygosity would influence tumor development and progression in MMTV-Wnt-1 oncomice or DMBA induced tumorigenicity, in a manner consistent with haploinsufficiency of the remaining allele.


METHODS
We crossed female SAFB1+/- (C57B6/129) mice with male MMTV-Wnt-1 (C57B6/SJL) mice to obtain SAFB1+/+/Wnt-1, SAFB1+/-/Wnt-1, and SAFB1+/- mice. For the chemical induced tumorigenesis study we treated 8 weeks old SAFB1+/- and SAFB+/+ BALB/c mice with 1 mg DMBA once per week for 6 weeks. Animals were monitored for tumor incidence and tumor growth. Tumors were characterized by performing H&E, and by staining for markers of proliferation and apoptosis.


RESULTS
We did not detect significant differences in tumor incidence and growth between SAFB1+/+/Wnt-1 and SAFB1+/-/Wnt-1 mice, and between DMBA-treated SAFB1+/+ and SAFB1+/-mice. Histological evaluation of tumors showed that SAFB1 heterozygosity did not lead to changes in proliferation or apoptosis. There were, however, significant differences in the distribution of tumor histologies with an increase in papillary and cribriform tumors, and a decrease in squamous tumors in the SAFB1+/-/Wnt-1 compared to the SAFB1+/+/Wnt-1 tumors. Of note, DMBA treatment resulted in shortened survival of SAFB1+/- mice compared to their wildtype littermates, however this trend did not reach statistical significance.


CONCLUSIONS
Our data show that SAFB1 heterozygosity does not influence Wnt-1 or DMBA-induced mammary tumorigenesis.
Kaipparettu
Benny Abraham
BA
Lester and Sue Smith Breast Center, Departments of Medicine, Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. kaippare@bcm.edu
Dobrzycka
Klaudia M
KM
Britton
Ora
O
Lee
Adrian V
AV
Herron
Alan J
AJ
Li
Yi
Y
Lewis
Michael T
MT
Medina
Daniel
D
Oesterreich
Steffi
S
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics* / Q000378:metabolism
D002273:Carcinogens; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C500609:scaffold attachment factor B1, mouse; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I