FOXA1: Growth inhibitor and a favorable prognostic factor in human breast cancer.
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.
Wolf
Ido
I
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA. wolfi@inter.net.il
Bose
Shikha
S
Williamson
Elizabeth A
EA
Miller
Carl W
CW
Karlan
Beth Y
BY
Koeffler
H Phillip
HP
D001940:Breast / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D044584:Carcinoma, Ductal / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D046888:Tissue Array Analysis; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C413374:p27 antigen