High folic acid diet enhances tumour growth in PyMT-induced breast cancer.
BACKGROUND
The B-vitamin folate is among the most studied bioactive food compound, and a dietary intake meeting the daily requirements has been found to reduce the risk of cancer and cardiovascular diseases as well as preventing neural tube defects during fetal development. Several countries have therefore introduced dietary fortification with folic acid. However, clinical and animal studies suggest that folic acid has a dual role in cancer development.


METHODS
During the period of initial tumour progression, MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice were fed with normal diet and high folic acid diet.


RESULTS
We found that PyMT-induced breast tumours highly express the cancer-specific folate receptor (FR), a feature they share with several human epithelial cancers in which expression of FRα correlates with tumour grade. Mice receiving a high folic acid diet displayed a significantly increased tumour volume compared with mice receiving normal diet. In the largest tumours, only found in mice on high folic acid diet, STAT3 was activated. In primary cells from PyMT tumours, STAT3 was activated upon treatment with folic acid in culture.


CONCLUSIONS
Our results offer a novel molecular explanation for folic acid-induced growth of existing tumours.
Department of Molecular Biology and Genetics, Aarhus University, Aarhus C 8000, Denmark.
Mariann Fagernæs
MF
Hansen
Department of Molecular Biology and Genetics, Aarhus University, Aarhus C 8000, Denmark.
Sarah Østrup
SØ
Jensen
Department of Molecular Biology and Genetics, Aarhus University, Aarhus C 8000, Denmark.
Ernst-Martin
EM
Füchtbauer
Department of Molecular Biology and Genetics, Aarhus University, Aarhus C 8000, Denmark.
Pia M
PM
Martensen
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000009:adverse effects* / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000178:diet therapy / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D011120:Polyomavirus / Q000235:genetics*; D050796:STAT3 Transcription Factor
D000952:Antigens, Polyomavirus Transforming; D058975:Folate Receptor 1; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D005492:Folic Acid