FoxA1 as a lineage-specific oncogene in luminal type breast cancer.
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 with previous data that FoxA1 is a marker of luminal cells in mammary gland, 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.
Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
Noritaka
N
Yamaguchi
Emi
E
Ito
Sakura
S
Azuma
Reiko
R
Honma
Yuka
Y
Yanagisawa
Akira
A
Nishikawa
Mika
M
Kawamura
Jun-Ichi
J
Imai
Kuniaki
K
Tatsuta
Jun-Ichiro
J
Inoue
Kentaro
K
Semba
Shinya
S
Watanabe
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009857:Oncogenes / Q000502:physiology
D014408:Biomarkers, Tumor; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D009363:Neoplasm Proteins