DIETARY MODULATION OF SEX STEROID ACTION
Focus on breast and prostate cancer

Organization:

Institute of Biomedicine & Functional Foods Forum
FI-20014 University of Turku, Finland

Research group:

Gabriela Chacon, MSc;  Niina Saarinen-Aaltonen, PhD

Main research objectives:

The main goal is to clarify the role of dietary factors in the development of hormone-dependent cancers. The focus is on altered sex steroid action, associated with obesity-related metabolic dysregulation, and its impact on the development of breast and prostate cancer. More specifically, we explore the mechanisms by which plant-derived polyphenols (such as lignans, stilbenoids and isoflavonoids) modulate estrogen action in normal and cancerous tissues.

Publications:

Yatkin E, Polari L, Laajala TD, Smeds A, Eckerman C, Holmbom B, Saarinen NM, Aittokallio T, Mäkelä SI: Novel Lignan and stilbenoid mixture shows anticarcinogenic efficacy in preclinical PC-3M-luc2 prostate cancer model. PLoS ONE 9(4): e93764. doi:10.1371/journal.pone.0093764. 2014.

Knuuttila M, Yatkin E, Kallio J, Savolainen S, Laajala TD, Aittokallio T, Oksala R, Häkkinen M, Keski-Rahkonen P, Auriola S, Poutanen M, Mäkelä S: Castration induces upregulation of intratumoral androgen biosynthesis and androgen receptor expression in orthotopic VCaP human prostate cancer xenograft model. Am J Path 184: 2163-73, 2014.

Elo T, Yu L, Valve E, Mäkelä S, Härkönen P: Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice. Endocr Relat Cancer 21: 677-690, 2014.

Polari L, Yatkin E, Martínez Chacón MG, Ahotupa M, Smeds A, Strauss L, Zhang F, Poutanen M, Saarinen N, Mäkelä SI: Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity. Mol Cell Endocrinol 412: 123-130, 2015.

Kibble M, Saarinen N, Tang J, Wennerberg K, Mäkelä S, Aittokallio T: Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Nat Prod Rep 32: 1249-1266, 2015.

Kibble M, Khan SA, Saarinen N, Iorio F, Saez-Rodriguez J, Mäkelä S, Aittokallio T: Transcriptional response networks for elucidating mechanisms of action of multitargeted agents. Drug Discov Today 21: 1063-75. doi: 10.1016/j.drudis.2016.03.001. 2016.

Ali I, Hurmerinta T, Nurmi T, Berglund M, Rüegg J, Poutanen M, Halldin K, Mäkelä S, Damdimopoulou P: From pure compounds to complex exposure: Effects of dietary cadmium and lignans on estrogen, epidermal growth factor receptor, and mitogen activated protein kinase signaling in vivo. Toxicol Lett 253: 27-35. doi: 10.1016/j.toxlet.2016.04.020. 2016

Laajala TD, Jumppanen M, Huhtaniemi R, Fey V, Kaur A, Knuuttila M, Aho E, Oksala R, Westermarck J, Mäkelä S, Poutanen M, Aittokallio T: Optimized design and analysis of preclinical intervention studies in vivo. Sci Rep 6: 30723, 2016

Knuuttila M, Mehmood A, Huhtaniemi R, Yatkin E, Häkkinen MR, Oksala R, Laajala TD, Ryberg H, Handelsman DJ, Aittokallio T, Auriola S, Ohlsson C, Laiho A, Elo LL, Sipilä P, Mäkelä SI, Poutanen M: Antiandrogens Reduce Intratumoral Androgen Concentrations and Induce Androgen Receptor Expression in Castration-Resistant Prostate Cancer Xenografts. Am J Pathol 188: 216-228. doi: 10.1016/j.ajpath.2017.08.036. 2018.

Martínez-Chacón G, Brown KA, Docanto MM, Kumar H, Salminen S, Saarinen N, Mäkelä S: IL-10 suppresses TNF-α-induced expression of human aromatase gene in mammary adipose tissue. FASEB J 32: 3361-3370. doi: 10.1096/fj.201700938RRR. 2018.

Knuuttila M, Mehmood A, Mäki-Jouppila J, Ryberg H, Taimen P, Knaapila J, Ettala O, Boström PJ, Ohlsson C, Venäläinen MS, Laiho A, Elo LL, Sipilä P, Mäkelä SI, Poutanen M: Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer. Endocr Relat Cancer 25: 807-819. doi: 10.1530/ERC-18-0148. 2018.

Huhtaniemi R, Oksala R, Knuuttila M, Mehmood A, Aho E, Laajala TD, Nicorici D, Aittokallio T, Laiho A, Elo L, Ohlsson C, Kallio P, Mäkelä S, Mustonen MVJ, Sipilä P, Poutanen M: Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts. Am J Pathol 188: 2890-2901. doi: 10.1016/j.ajpath.2018.07.029. 2018.

Principal Investigators
Sari Mäkelä, MD, PhD
Professor of Biomedicine
sarmak(at)utu.fi

Niina Saarinen, PhD
Senior Scientist
nisaarin(at)utu.fi

Institute of Biomedicine & Functional Foods Forum

Sari Mäkelä