TY - JOUR
T1 - FOXA1
T2 - Growth inhibitor and a favorable prognostic factor in human breast cancer
AU - Wolf, Ido
AU - Bose, Shikha
AU - Williamson, Elizabeth A.
AU - Miller, Carl W.
AU - Karlan, Beth Y.
AU - Koeffler, H. Phillip
PY - 2007/3/1
Y1 - 2007/3/1
N2 - The transcription factor Forkhead-box A1 (Foxa1), a member of the FOX class of transcription factors, has been implicated in the pathogenesis of lung, esophageal and prostate cancers. We have recently identified transcriptional activation of p27 by FOXA1. In this study, we analyzed the activities and expression pattern of FOXA1 in breast cancer. Forced expression of FOXA1 inhibited clonal growth of breast cancer cell lines, and FOXA1 levels inversely correlated with growth stimuli. In the estrogen receptor (ER)-positive MCF-7 cells, FOXA1 increased p27 promoter activity and inhibited the ER pathway activity. Analysis of FOXA1 expression in breast tissue arrays revealed significantly higher expression in pure ductal carcinomas in situ compared to invasive ductal carcinomas (IDC); and in IDC, high expression of FOXA1 was associated with favorable prognostic factors. Yet, FOXA1 expression was noted in a subset of the ER-negative tumors. Taken together, our findings suggest a growth inhibitory role for FOXA1, and identify it as a novel, potential prognostic factor in breast cancer.
AB - The transcription factor Forkhead-box A1 (Foxa1), a member of the FOX class of transcription factors, has been implicated in the pathogenesis of lung, esophageal and prostate cancers. We have recently identified transcriptional activation of p27 by FOXA1. In this study, we analyzed the activities and expression pattern of FOXA1 in breast cancer. Forced expression of FOXA1 inhibited clonal growth of breast cancer cell lines, and FOXA1 levels inversely correlated with growth stimuli. In the estrogen receptor (ER)-positive MCF-7 cells, FOXA1 increased p27 promoter activity and inhibited the ER pathway activity. Analysis of FOXA1 expression in breast tissue arrays revealed significantly higher expression in pure ductal carcinomas in situ compared to invasive ductal carcinomas (IDC); and in IDC, high expression of FOXA1 was associated with favorable prognostic factors. Yet, FOXA1 expression was noted in a subset of the ER-negative tumors. Taken together, our findings suggest a growth inhibitory role for FOXA1, and identify it as a novel, potential prognostic factor in breast cancer.
KW - Breast cancer
KW - Estrogen receptor
KW - FOXA1
KW - p27
UR - http://www.scopus.com/inward/record.url?scp=33846804242&partnerID=8YFLogxK
U2 - 10.1002/ijc.22389
DO - 10.1002/ijc.22389
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C2 - 17163418
AN - SCOPUS:33846804242
SN - 0020-7136
VL - 120
SP - 1013
EP - 1022
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 5
ER -