We study pathways that control prostate cancer and novel approaches for managing this disease during therapy resistance. We are defining roles for 1) intratumoral androgen receptor (AR); 2) interplay between AR-dependent and AR-independent pathways. One immediate goal entails correlating expression of androgen biosynthetic enzymes in patient tumor samples to disease outcome. We showed that the androgen-inactivating enzyme SULT2B is expressed at markedly reduced levels in prostate cancer. This result is highly significant given its implication in androgen-regulated prostate cancer growth. In light of the known anti-prostate cancer activity of vitamin D, SULT2B induction by vitamin D is also intriguing. The second focus is to define a drug-mediated targeting approach that integrates inactivation of both the PI3K/AKT/mTORC1 axis and AR-mediated signaling.
Seo YK, Mirkheshti N, Song CS, Kim S, Dodds S, Ahn SC, Christy B, Mendez-Meza R, Ittmann MM, Abboud-Werner S, Chatterjee B. SULT2B1b sulfotransferase: induction by vitamin D receptor and reduced expression in prostate cancer. Mol Endocrinol. 2013 Jun;27(6):925-39.
Kim KY, Cho HJ, Yu SN, Kim SH, Yu HS, Park YM, Mirkheshti N, Kim SY, Song CS, Chatterjee B, Ahn SC. Interplay of reactive oxygen species, intracellular Ca2+ and mitochondrial homeostasis in the apoptosis of prostate cancer cells by deoxypodophyllotoxin. J Cell Biochem. 2013 May;114(5):1124-34.
Echchgadda I, Chang TH, Sabbah A, Bakri I, Ikeno Y, Hubbard GB, Chatterjee B, Bose S. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): consequences of deficient interferon-dependent antiviral defense. BMC Cancer. 2011 Jan 28;11:43.
Ko S, Ahn J, Song CS, Kim S, Knapczyk-Stwora K, Chatterjee B. Lysine methylation and functional modulation of androgen receptor by Set9 methyltransferase. Mol Endocrinol. 2011 Mar;25(3):433-44.
Shi L, Ko S, Kim S, Echchgadda I, Oh TS, Song CS, Chatterjee B. Loss of androgen receptor in aging and oxidative stress through Myb protooncoprotein-regulated reciprocal chromatin dynamics of p53 and poly(ADP-ribose) polymerase PARP-1. J Biol Chem. 2008 Dec 26;283(52):36474-85.