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the impact of diet on differentiated breast tissue: how polarized cells may lose sense of direction in initial stages of cancer development
Author(s) -
Chaboub Lesley S,
Metcalf Kelly,
Retseck Elizabeth,
Chandramouly Guruchankar,
Lelièvre Sophie A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a79-a
Subject(s) - polarity (international relations) , cell polarity , breast cancer , cancer , epithelial polarity , biology , medicine , chemistry , microbiology and biotechnology , cell , biochemistry
Apical polarity is a feature of epithelial differentiation lost in early stages of breast neoplasia. Our recent work has linked the lack of apical polarity to the priming of breast epithelial cells for cell cycle entry, thus suggesting a key role for apical polarity alterations in initial phases of cancer. However, factors influencing apical polarity remain poorly understood. High fatty acid ω6/ω3 ratios (25/1 to 50/1) have been associated to increased risks of breast cancer whereas low ratios (10/1–1/1) and vitamin D have been associated to lower risks and/or protective effects. In this work we are investigating whether the dietary factors that influence breast cancer risk may control apical polarity. Using three‐dimensional cell culture of breast epithelial cells that mimic the formation of tissue‐like breast epithelial structures (acini) we have identified apical polarity markers, like Pals‐1 and PAR‐3, that help specify the degree of apical polarity alteration. Results show that a 4‐day treatment with ω6 arachidonic acid induces profound alterations in apical polarity in a significant portion of acini, and that there is a trend towards apical polarity loss with a 15/1 ω6/ω3 ratio. Current studies are comparing long‐term culture with different ratios of fatty acids and assessing a potential protective effect of vitamin D. Work supported by the NIH/NCI and the Purdue Oncological Sciences Center.