Table 2. differentially modulated by Bombesin and DHT Official Process Classification Symbol Name Gene ID Function Genes Up-regulated by Bombesin

inflammation MT2A5,* metallothionein 2A 4502 copper ion homeostatsis folding MT1H metallothionein 1H 4496 heavy metal binding protein signal transduction GRB10 growth factor receptor-bound 2887 adapter protein involved in protein 10 RTK signaling, insulin receptor and insulin-like growth factor receptors transcription factor CEBPB CCAAT/enhancer binding 1051 bzip transcription factor protein (C/EBP), beta GTF2E15,8 general transcription factor 2960 general transcription factor IIE, polypeptide 1, alpha machinery 56kDa MYC1,5,* v-myc myelocytomatosis viral 4609 involved in cell cycle homolog (avian) progression, apoptosis and cell transformation PITX1 paired-like homeodomain 5307 involved in morphogenesis transcription factor 1 and skeletal development unknown RetSat all-trans-13, 14-dihydroretinol 54884 unknown saturase

Genes Down-regulated by Bombesin

androgen-regulated PPAP2A phosphatidic acid 8611 role in hydrolysis and phosphatase type 2A uptake of from extracellular space apoptosis TRAF4 TNF receptor-associated 9618 anti-apoptotic, interacts with factor 4 p75NTR, activator of MAPK8/JNK RYBP* RING1 and YY1 binding 23429 for the YY1 and protein E4TF1/hGABP transcription factors, promotes apoptosis in cancer cells TGM2 2 (C 7052 catalyzes crosslinking of polypeptide, protein- protein, induced by retinoic -gamma- acid, appears to be involved glutamyltransferase in apoptosis cholesterol HMGCR1,5 3-hydroxy-3-methylglutaryl- 3156 rate limiting for coenzyme A reductase cholesterol synthesis IDI1 isopentenyl-diphosphate delta 3422 catalyzes interconversion of iPP to DMAPP leading to cholesterol formation INSIG11 insulin induced gene 1 3638 ER membrane protein, regulates cholesterol concentration in cells LDLR low density lipoprotein 3949 receptor mediated receptor (familial endocytosis hypercholesterolemia) SC4MOL1 sterol-C4-methyl oxidase-like 6307 ER localized, cholesterol biosynthesis endocytosis IGF2R* insulin-like growth factor 2 3482 transmembrane protein, receptor receptor for IGFII and M6P, sorts lysomal metabolism ACACA1 acetyl-coenzyme A 31 catalyzes rate limiting step carboxylase alpha in ACSL3 acyl-CoA synthetase long- 2181 and chain family member 3 biosynthesis FASN3,* fatty acid 2194 catalyzes synthesis of palmitate ion transport SLC22A3* solute carrier family 22, 6581 cation transporter member 3 metabolism MAT2A* methionine 4144 essential cellular enzyme adenosyltransferase II, alpha responsible for S- adenosylmethionine biosythesis OGDH oxoglutarate (alpha- 4967 catalyzes conversion of 2- ketoglutarate) oxoglutarate to succinyl- (lipoamide) CoA and CO2 during Kreb cycle SQLE squalene epoxidase 6713 rate limiting enzyme for sterol biosynthesis mitosis ARL10C ADP-ribosylation factor-like 55207 GTPase associated with 10C microtubules and involved in chromosomal segregation mRNA processing PTBP1 polypyrimidine tract binding 5725 hnRNP associated with pre protein 1 mRNA, part of splicing machinery SFRS51,* splicing factor, arginine/serine 6430 involved in mRNA splicing rich 5 protein folding CANX1,* calnexin 821 molecular chaperone for glycoproteins, Ca++ binding, ER associated HSPA4* heat shock 70kDa protein 4 3308 chaperone protein TRA11,* tumor rejection antigen (gp96) 7184 chaperone protein, HSP96 1 signal transduction PBEF1 pre-B-cell colony enhancing 10135 secreted cytokine-like factor 1 protein, regulates NAD+ dependent deacetylase activity, has anti-apoptotic properties CAMKK22,6 /calmodulin- 10645 serine/threonine protein dependent protein kinase kinase, phosphorylates kinase 2, beta CaMK1 and CaMK4 LRIG1 leucine-rich repeats and 26018 downregulateion and immunoglobulin-like domains degradation of EGFRs, 1 downregulation of LRIG1 associated with cancers transcription factor TSC22D1 TSC22 domain family, 8848 early response gene, member 1 modulates TGF-beta signaling, binds to and modulates Smad3 and 4 transcriptional activity unknown ABHD2 abhydrolase domain 11057 putative enzyme containing 2 RBM16 RNA binding motif protein 16 22828 unknown SE20-4 cutaneous T-cell lymphoma- 64061 coilin interacting protein, associated tumor antigen possibly involved with Cajal se20-4 bodies

1-9 Additional reference of androgen regulated genes 1 DePrimo SE, et al. (2002) Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome Biology 3,research0032.1-0032.12 2 Nelson PS, et al. (2002) The program of androgen-responsive genes in neoplastic prostate epithelium. PNAS 99, 11890- 11895 3 Segawa T, et al. (2002) Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells. Oncogene 21, 8749-8758 4 Stanbrough M, et al. (2006) Increased expression of genes converting adrenal androgens to testosterone in androgen- independent prostate cancer. Cancer Res. 66, 2815-2825 5 Velasco AM, et al, (2004) Identification and validation of novel androgen-regulated genes in prostate cancer. Endocrinology 145, 3913-3924 6 Xu LL, et al. (2001) Quantitative expression profile of androgen regulated genes in prostate cancer cells and identification of prostate specific genes. Int. J. Cancer 92, 322-328 7 York TP, et al. (2005) cDNA microarray analysis identifies genes induced in common by growth factors and androgen in human prostatic epithelial cells. Molecular Carcinogenesis 44, 242-251 8 Masuda K, et al. (2005) Androgen receptor binding sites identified by a GREF_GATA model. J. Mol. Biol. 353, 763-771 9 Rae JM, et al. (2006) GREB1 is a novel androgen-regulated gene required for prostate cancer growth. Prostate 66, 886-894 * Genes regulated by MYC Zeller KI, et al. (2003) An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biology 4, R69.1-R69.10