SEMINAIRES « Institut André LWOFF » - SFR

1. SEMINAIRES « Institut André LWOFF » - SFR Hôpital Paul Brousse, Amphithéâtre Pierre Barret du CHB - 2ème étage 12-14 avenue Paul Vaillant Couturier  94804 Villejuif Cedex www.vjf.cnrs.fr/newial Vous trouverez ci-dessous un abstract concernant le séminaire du Dr Jeff Holst (Centenary Institute à Sydney) le 5 septembre 2011. « Nutrition and Prostate Cancer: Molecular mechanisms co-ordinating amino acid transport and mTORC1 signaling  » Abstract L-type amino acid transporters such as LAT1 and LAT3 mediate uptake of essential amino acids such as leucine. Here we report that prostate cancer cells coordinate the expression of LAT1 and LAT3, thereby maintaining sufficient levels of leucine for mTORC1 signaling and cell growth. We show that inhibition of LAT function leads to decreased cell growth and mTORC1 signaling in prostate cancer cells. These cells maintain amino acid influx via androgen receptor regulation of LAT3 expression, and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses are intact in primary prostate cancer, as indicated by high levels of LAT3 in primary disease, and an increase in LAT1 following hormone ablation and in metastatic lesions. These data show that prostate cancer cells respond to the demand for increased amino acids through an integrated pathway, leading to increased amino acid transporter expression and cell growth. Résumé de sa carrière Dr Holst completed his Bachelor of Science (Honours) at the University of Technology, Sydney, and PhD in 2003 at the Centre for Immunology, St Vincent’s Hospital and the University of NSW. He went on to complete a successful postdoc in the USA at St Jude Children’s Research Hospital, where he examined T cell receptor signaling, with first author publications in Nature Immunology, NatureMethods, Nature Protocols as well as publications in EMBO Journal and Journal of Immunology.