Lab Focus: Mechanisms of Chemoprevention by Dietary Fatty Acids
We are currently investigating the molecular mechanisms by which CLA prevents tumor promotion in epithelial tissues.

Dr. Thuillier’s research combines studies of molecular mechanisms for how dietary nutrients function in cancer with prevention approaches to carcinogenesis. The main interest in the lab is to study the role of dietary fatty acids in cancer prevention. The lab has two tracts, a basic research module and a molecular epidemiology focus. The main project is concerned with exploring a novel approach to the prevention and control of epithelial cancers. The principal current focus is the use of dietary fatty acids that have been shown to block or decrease skin tumor development. Understanding the molecular mechanisms by which these fatty acids protect from skin tumor development would help in making better recommendations on increased consumption of these fatty acids for the purpose of nutritional intervention and/or chemoprevention. Addition of these fatty acids to the diet could be advantageous for the many millions of individuals who suffer from skin cancer every year. We previously established that conjugated linoleic acid (CLA) has an inhibitory effect on skin tumor promotion in mice subjected to a two-stage carcinogenesis model. Although the preventive effect of CLA on tumorigenesis are well established, very little is known about the molecular mechanisms involved. Our goal is to study those mechanisms and determine the target for the action of CLA. Some of these targets include the peroxisome proliferators activated receptors (PPARs), regulation of apoptosis, oxidative stress, epigenetic events and DNA repair. Furthermore, we are interested in determining the contribution of CLA to keratinocyte differentiation and proliferation and to skin tumor prevention. Finally, we are interested in studying the role that dietary n-3 fatty acids may exert on cancer prevention.

In a second project, we are elucidating the effect of CLA on body mass index in an overweight population. This clinical trial will specifically determine whether CLA could be beneficial in reducing BMI in this population. An additional end-point of the study will evaluate the effect of CLA on oxidative stress in that same population.

Finally, in a third project we are investigating the effect of CLA on breast and prostate cancer prevention. Specifically, we have determined that CLA up-regulates the tumor suppressor gene BRCA1 expression. Hence, we will be looking at the effect of CLA on BRCA1 expression in cells from breast cancer and uterine cancer patients that have been shown to be low BRCA1 expressor.

Selected Publications
Clarke, S. D., Thuillier, P., Baillie, R. A., X, Sha. (1999). Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors. Am J Cli Nutr 70(4): 566-571.

*Muga, S. J., *Thuillier, P., Pavone, A., Rundhaug, J. E., Jisaka, M., Boeglin, W., Brash, A. R., and Fischer, S. M. (2000). 8(S)-Lipoxygenase products activate PPARÿÿand induce differentiation in murine keratinocytes. Cell Growth & Diff. 11: 447-454 (* equivalent co-authorship)

Thuillier, P., Anchiraico, G. J., Nickel, K. P., Maldve, R. E., Gimenez-Conti, I., Muga, S. J., Liu, Kai-Li, Fischer, S. M., and Belury, M. A. (2000) Peroxisome proliferator activated receptor (PPAR) alpha activators inhibit mouse skin tumor promotion. Molec Carcinogenesis 29(3): 134-142.

Kehrer, J. P., Biswal, S., Thuillier, P., Datta, K., Vanden Heuvel, J. P., and Fischer, S. M. (2001) Inhibition of peroxisome proliferator activated receptor alpha by MK886. Biochem J 356: 899-906.

N. Liu, W.Qiang, X. Kuang, P. Thuillier, W.S. Lynn, P.K.Y. Wong. (2002) The peroxisome proliferator phenylbutyric acid (PBA) protects astrocytes from ts1 MoMuLV-induced oxidative cell death. J Neuro Virol 8: 320-327.