Research Project
Grant-in-Aid for Scientific Research (C)
The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells.Almost 20% of cancer cells show constitutive NF-кB activity, which induce expression of several genes involved in tumor growth, metastasis and angiogenesis, however, the mechanism of the constitutive activation is unclear. To answer this question, we first evaluated basal NF-кB activities of 125 human cancer cell lines from various tissues with electorophoretic mobility shift assays. We are analyzing the mechanism using the cell lines showing high NF-кB activity.
All 2008 2007 2006 Other
All Journal Article (11 results) (of which Peer Reviewed: 6 results) Presentation (10 results) Remarks (1 results)
Cancer Res 68
Pages: 1881-1888
Biochem Biophys Res Commun 365
Pages: 711-717
FEBS Lett 581
Pages: 3909-3914
BMC Bioinformatics 8
Pages: 15-15
Mol. Cell. Proteomics (in press)
http://www.biomed.sci.waseda.ac.jp/