Biomarkers of Response to PI3K Inhibitors Table 1. List of top-scoring genes that are up-regulated in GDC-0941-resistant or GDC-0941-sensitive tumor cell lines. mRNA Upregulated in GDC-0941 Sensitive Cell Lines Gene Symbol Gene Name T-Test 3.99 3.31 3.18 2.97 2.87 2.87 2.76 2.50 2.46 2.36 2.33 2.27 2.23 2.13 1.92 1.85 1.81 1.79 1.75 1.72 T-Test 25.81 25.44 25.37 24.42 24.30 23.43 23.33 23.21 23.21 23.18 23.11 23.04 23.01 22.99 22.96 22.93 22.91 22.90 22.90 22.89 P-Value 5.99E203 7.98E203 5.99E203 5.99E203 5.99E203 5.99E203 5.99E203 5.99E203 7.98E203 5.99E203 7.98E203 5.99E203 5.99E203 5.99E203 5.99E203 7.98E203 7.98E203 7.98E203 5.99E203 5.99E203 P-Value 2.00E203 2.00E203 9.98E203 2.00E203 2.00E203 7.98E203 2.00E203 2.00E203 2.00E203 9.98E203 2.00E203 2.00E203 2.00E203 2.00E203 9.98E203 2.00E203 9.98E203 2.00E203 2.00E203 2.00E203 VAV3 DGKE MBD1 SERP1 TXNL1 NLGN4X C1ORF91 SLC25A1 ZBTB40 FAM51A1 LOC116349 KIAA1468 PIGN PKD1L1 SELT CISH MGC50559 NPY5R PEX10 C6ORF35 TRIM50C GALR2 INSL3 LOC389633 GTPBP10 PGRMC1 DNASE1L3 CACNG2 FAM90A1 OGT FKBP6 GDAP1L1 CHRNB1 NLGN3 ZNF259 DDN NXF3 MGC35366 TANK LOC116123 vav 3 oncogene diacylglycerol kinase, epsilon 64 kDa methyl-CpG binding domain protein 1 stress-associated endoplasmic reticulum protein 1 thioredoxin-like 1 neuroligin 4, X-linked chromosome 1 open reading frame 91 solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1 zinc finger and BTB domain containing 40 family with sequence similarity 51, member A1 hypothetical protein BC014011 KIAA1468 phosphatidylinositol glycan, class N polycystic kidney disease 1 like 1 selenoprotein T cytokine inducible SH2-containing protein hypothetical protein MGC50559 neuropeptide Y receptor Y5 peroxisome biogenesis factor 10 chromosome 6 open reading frame 35 tripartite motif-containing 50C galanin receptor 2 insulin-like 3 (Leydig cell) similar to FLJ10408 protein GTP-binding protein 10 progesterone receptor membrane component 1 deoxyribonuclease I-like 3 calcium channel, voltage-dependent, gamma subunit 2 family with sequence similarity 90, member A1 O-linked N-acetylglucosamine (GlcNAc) transferase FK506 binding protein 6, 36 kDa ganglioside-induced differentiation-associated protein 1-like 1 cholinergic receptor, nicotinic, beta polypeptide 1 (muscle) neuroligin 3 zinc finger protein 259 dendrin nuclear RNA export factor 3 hypothetical protein MGC35366 TRAF family member-associated NFKB activator hypothetical protein BC014341 mRNA Upregulated in GDC-0941 Resistant Cell Lines Gene Symbol Gene Name doi:10.1371/journal.pone.0046518.t001 pathways. Amongst all effectors analyzed (not shown), increased phosphorylation of the cell cycle checkpoint regulator Chk2 was observed in both the MDA-MB-231 and OVCAR-4 cell lines upon treatment with GDC-0941 and OGT siRNA (Fig. 4D and 4H). To further investigate the role of OGT in regulating sensitivity to inhibitors of the PI3K pathway, we next analyzed the effects that the loss of OGT expression had on tumor cell line sensitivity to the dual PI3K/mTOR inhibitor, NVP-BEZ235 [28]. PLOS ONE | www.plosone.org 6 September 2012 | Volume 7 | Issue 9 | e46518