TY - JOUR
T1 - Frequent activation of CArG binding factor-A expression and binding in N-methyl-N-nitrosourea-induced rat mammary carcinomas
AU - Mikheev, Andrei M.
AU - Inoue, Akira
AU - Jing, Lichen
AU - Mikheeva, Svetlana A.
AU - Li, Vivian
AU - Leanderson, Tomas
AU - Zarbl, Helmut
N1 - Funding Information:
We thank Yuan Gao for the assistance with animal handling, mammary tissue dissection and histology. This research was supported by funding from US Army Medical Research and Materiel Command under DAMD17-98-1-8086, and by the UW NIE-HS sponsored Center for Ecogenetics and Environmental Health, Grant #: NIEHS P30ES07033. T.L. is supported by the Swedish Medical Research Council and the Swedish Cancer Foundation.
PY - 2004/11
Y1 - 2004/11
N2 - We previously identified a positive transcriptional element identical to human Ha-ras response element (HRE) within the promoter of the rat Ha-ras gene. We further identified CArG binding factor A (CBF-A), a member of heterogeneous nuclear ribonuclear protein (hnRNP) gene family, as a trans-acting factor that binds the HRE sequence with high affinity in rat mammary carcinoma cells. To determine if activation of CBF-A plays a role in tumor development in vivo, we investigated CBF-A expression and binding activity in rat mammary tumors induced by N-methyl- N-nitrosourea. We found that \sim 82% of tumors expressed CBF-A at levels that were 3-20 fold higher than detected in normal mammary gland. Moreover, elevated CBF-A protein levels were invariably associated with increased binding activity to the HRE. CBF-A mRNA levels in tumors were on average elevated only two fold as compared to normal mammary gland, indicating that increased CBF-A protein levels in tumors resulted from both translational and/or post-translational regulation. The level of CBF-A expression in mammary tumors was independent of Ha-ras mutational status. Together, these findings indicated that deregulation of CBF-A contributes to mammary carcinogenesis via a mechanism that is distinct from its hnRNP functions in binding and post-transcriptional regulation of RNA.
AB - We previously identified a positive transcriptional element identical to human Ha-ras response element (HRE) within the promoter of the rat Ha-ras gene. We further identified CArG binding factor A (CBF-A), a member of heterogeneous nuclear ribonuclear protein (hnRNP) gene family, as a trans-acting factor that binds the HRE sequence with high affinity in rat mammary carcinoma cells. To determine if activation of CBF-A plays a role in tumor development in vivo, we investigated CBF-A expression and binding activity in rat mammary tumors induced by N-methyl- N-nitrosourea. We found that \sim 82% of tumors expressed CBF-A at levels that were 3-20 fold higher than detected in normal mammary gland. Moreover, elevated CBF-A protein levels were invariably associated with increased binding activity to the HRE. CBF-A mRNA levels in tumors were on average elevated only two fold as compared to normal mammary gland, indicating that increased CBF-A protein levels in tumors resulted from both translational and/or post-translational regulation. The level of CBF-A expression in mammary tumors was independent of Ha-ras mutational status. Together, these findings indicated that deregulation of CBF-A contributes to mammary carcinogenesis via a mechanism that is distinct from its hnRNP functions in binding and post-transcriptional regulation of RNA.
KW - CArG binding factor A
KW - heterogeneous nuclear ribonuclear protein
KW - mammary tumor
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U2 - 10.1007/s10549-004-1280-5
DO - 10.1007/s10549-004-1280-5
M3 - Article
C2 - 15538050
AN - SCOPUS:8744220668
SN - 0167-6806
VL - 88
SP - 95
EP - 102
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -