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Does KLF4 mediate the anticarcinogenic activity of sulforaphane?

Reference	BB/C509066/1
Principal Investigator / Supervisor	Professor Richard Mithen
Co-Investigators / Co-Supervisors	Dr Ian Johnson, Dr Elizabeth Lund
Institution	Quadram Institute Bioscience
Department	Nutrition Division
Funding type	Research
Value (£)	259,440
Status	Completed
Type	Research Grant
Start date	01/11/2004
End date	31/10/2007
Duration	36 months

Abstract

A diet rich in cruciferous vegetables is associated with a reduction in risk of cancer. These vegetables contain a group of sulphur containing compounds called glucosinolates that degrade to isothiocyanates following consumption. When the human colon carcinoma cell line CaCo2 is exposed to physiologically appropriate concentrations of sulforaphane, (4- methylsulphinylbutyl isothiocyanate, derived from broccoli) 125 genes are upregulated (P less than 0.001). Amongst these is the KLF4 transcription factor. Expression of KLF4 has been shown to be associated with antiproliferative activity via induction of p21 and other genes involved with suppression of cell cycle and DNA synthesis, and also with the differentiation of goblet cells within the intestinal tract. Allyl isothiocyanate, another common food-borne isothiocyanate, does not induce KLF4. We wish to develop stable KLF4 knockout CaCo2 cell lines via RNAi approaches, and use these to see which genes are transcriptionally regulated by KLF4 following sulforaphane exposure. APC min mice have a mutant APC allele, resulting in low levels of expression of KLF4, and a high incidence of intestinal tumours. We wish to investigate if a sulforaphane-enriched diet will lead to the induction of KLF4 in APCmin mice, an increase in the number of goblet cells and a reduction in the numbers and growth of tumours. Lastly, we wish to compare KLF4, goblet cell expression and carcinogenesis in APC min mice fed a broccoli-enriched or a mustard-enriched diet, the latter containing high levels of allyl isothiocyanate.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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