Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital

Table 2

Differentially expressed proteins identified by LC-MS/MS in the liver tumors, surrounding and normal-appearing liver tissue of Ogg1^−/− and Ogg1^+/+ mice treated with PB for 78 weeks.

Protein name (symbol)	GI number	Ogg1^−/− versus Ogg1^+/+ liver		PB, Ogg1^−/− liver		PB, Ogg1^+/+ liver		Ogg1^−/− HCC		Ogg1^+/+ HCA
		Ratio	value	Ratio	value	Ratio	value	Ratio	value	Ratio	value	Location	Function(s)/upstream regulator
Cytochrome P450 fam. 2 subfam. E mem. 1 (CYP2E1)	461828	-	-	-	-	-	-	3.26	0.00	1.54	0.00	EPR	XM/CTNNB1
Cytochrome b5 type A (CYB5A)	3023608	-	-	1.65	0.00	1.64	0.00	1.41	0.00	1.43	0.00	EPR	FAM/CTNNB1
Cytochrome P450 fam. 1 subfam. A mem. 2 (CYP1A2)	117146	0.87	0.03	2.79	0.00	2.03	0.00	1.40	0.01	2.36	0.00	EPR	XM/PXR, CAR
Cytochrome P450 fam. 2 subfam. F mem. 2 (CYP2F2)	461829	0.89	0.03	1.23	0.03	-	-	2.04	0.01	0.14	0.02	EPR	XM, SM/CAR
Cytochrome P450 fam. 2 subfam. A mem. 5 (CYP2A5)	117196	1.42	0.00	2.57	0.00	3.23	0.00	1.68	0.00	1.84	0.00	EPR	XM/PXR, CAR
Cytochrome P450 fam. 2 subfam. B mem. 10 (CYP2B10)	117215	-	-	3.78	0.00	4.58	0.01	2.48	0.00	-	-	EPR	XM/CAR, PXR
Cytochrome P450 fam. 3 subfam. A mem. 11 (CYP3A11)	5921911	-	-	2.06	0.00	2.08	0.00	2.59	0.02	-	-	EPR	XM/PXR, CAR
Carboxylesterase 1 (CES1)	57013389	1.20	0.00	1.26	0.00	1.24	0.00	2.90	0.00	0.85	0.00	EPR	XM, TgM/PXR
Glutamate-ammonia ligase, glutamine synthetase (GLUL)	145559476	0.80	0.00	1.60	0.04	2.81	0.01	2.72	0.00	2.39	0.00	C	GABAM/PXR
Transferrin (TF)	21363012	-	-	1.23	0.00	1.38	0.00	0.67	0.00	1.26	0.00	ES	CIIH, AFO/PXR
Sulfotransferase fam. 1A. mem. 1 (Sult1a1)	1711570	1.28	0.00	0.69	0.00	1.20	0.02	2.48	0.00	1.56	0.00	C	XM, SM/CAR
Cytochrome P450 oxidoreductase (POR)	548338	1.20	0.00	1.38	0.00	1.92	0.00	1.76	0.00	1.29	0.00	EPR	CRH/PXR, CAR
Superoxide dismutase 1, soluble (SOD1)	134614	-	-	0.93	0.02	0.92	0.04	1.20	0.00	1.31	0.00	C	CRH/Nrf2
Thioredoxin (TXN)	549078	-	-	-	-	1.22	0.03	-	-	1.39	0.05	C	CRH/Nrf2
Peroxiredoxin 1 (PRDX1)	547923	0.85	0.01	1.20	0.00	1.25	0.00	1.25	0.00	2.19	0.00	C	CRH/Nrf2
Glutathione S-transferase, alpha 3 (GSTA3)	232203	-	-	-	-	1.23	0.01	1.26	0.01	2.53	0.00	C	GM/Nrf2, PXR, CAR
Glutathione S-transferase, alpha 4 (GSTA4)	20141353	-	-	1.73	0.01	1.61	0.02	0.68	0.01	2.05	0.00	O	GM/Nrf2, PXR, CAR
Glutathione S-transferase, mu 1 (GSTM1)	121718	-	-	2.31	0.00	2.70	0.00	1.36	0.01	4.40	0.00	Mit	GM/Nrf2, PXR, CAR
Glutathione S-transferase, mu 3 (GSTM3)	121720	-	-	3.99	0.00	6.08	0.00	1.38	0.01	3.61	0.00	C	GM/Nrf2, PXR, CAR
Glutathione S-transferase, mu 5 (GSTM5)	121716	-	-	2.59	0.00	3.07	0.00	-	-	2.06	0.00	C	GM/Nrf2, PXR, CAR
Microsomal glutathione S-transferase 1 (MGST1)	47116030	0.72	0.00	1.20	0.05	-	-	1.50	0.00	0.73	0.01	EPR	GM/PXR
Glutathione S-transferase, pi 1 (GSTP1)	121747	0.76	0.00	-	-	0.64	0.00	0.71	0.00	0.69	0.00	C	GM/Nrf2
UDP-glucose 6-dehydrogenase (UGDH)	6136117	-	-	1.74	0.02	1.70	0.02	0.69	0.00	1.68	0.00	N	CM/Nrf2
Arginase 1 (ARG1)	2492934	-	-	0.71	0.00	0.81	0.00	1.39	0.00	0.15	0.00	C	M, UC
Carbamoyl-phosphate synthase 1 (CPS1)	73918911	0.96	0.01	0.75	0.00	0.77	0.00	1.40	0.00	0.19	0.00	C	M, UC
Argininosuccinate lyase (ASL)	21263402	-	-	0.81	0.00	0.88	0.02	1.55	0.00	0.23	0.00	C	M, UC
Ornithine carbamoyltransferase (OTC)	129277	0.91	0.04	0.89	0.01	0.77	0.00	1.24	0.00	0.11	0.00	C	M, UC
Argininosuccinate synthase 1 (ASS1)	114290	0.84	0.00	0.72	0.00	0.78	0.00	2.45	0.00	0.14	0.00	C	M, UC
Cytochrome P450, fam. 2, subfam. c, mem. 54 (CYP2C54)	81893400	-	-	2.90	0.00	1.99	0.00	4.32	0.03	0.56	0.02	EPR	XM, FAM/PPARA
Cytochrome P450, fam. 2, subfam. c, mem. 70 (CYP2C70)	83288029	0.71	0.03	1.33	0.01	-	-	2.06	0.03	0.73	0.00	EPR	XM, SM/PPARA
Cytochrome c oxidase subunit II (MT-CO2)	117029	-	-	-	-	-	-	1.28	0.00	0.30	0.00	Mit	CRH, FABO/PPARA
4-Hydroxyphenylpyruvate dioxygenase (HPD)	83303597	0.88	0.01	-	-	-	-	2.05	0.00	0.64	0.00	C	TyrM/PPARA
Glycine N-methyltransferase (GNMT)	55976615	0.86	0.00	0.75	0.00	0.89	0.00	2.19	0.00	0.31	0.00	C	GlyM/PPARA
Glycine-N-acyltransferase (GLYAT)	81879668	-	-	-	-	0.87	0.00	1.29	0.01	0.79	0.02	C	GlyM
Indolethylamine N-methyltransferase (INMT)	731019	-	-	1.33	0.00	0.77	0.03	1.80	0.00	0.31	0.03	C	AM
Paraoxonase 1 (PON1)	1709718	-	-	1.77	0.00	2.00	0.01	7.38	0.00	-	-	ES	XM, ChM/PPARG
Vimentin (VIM)	138536	-	-	1.42	0.05	-	-	1.66	0.01	-	-	C	IFO, A(−)
Phosphoenolpyruvate carboxykinase 1 (PCK1)	18203662	-	-	0.60	0.02	-	-	2.63	0.03	-	-	C	CM/PPARG
Peroxiredoxin 2 (PRDX2)	2499469	-	-	-	-	-	-	0.73	0.01	-	-	C	CRH/ERBB2. MYC
Peroxiredoxin 3 (PRDX3)	126986	-	-	1.16	0.03	1.13	0.05	0.59	0.00	2.36	0.00	Mit	CRH
Peroxiredoxin 5 (PRDX5)	20141789	0.87	0.04	-	-	0.88	0.02	0.78	0.01	-	-	Mit	CRH
Peroxiredoxin 6 (PRDX6)	3219774	-	-	-	-	-	-	0.80	0.00	1.75	0.00	L	CRH, LC
Ubiquinol-cytochrome c reductase, Rieske iron–sulfur polypeptide 1 (UQCRFS1)	52000877	-	-	-	-	-	-	1.33	0.04	-	-	Mit	XM/RICTOR
Electron transfer flavoprotein alpha subunit (ETFA)	146345417	-	-	0.79	0.00	0.78	0.00	1.32	0.00	-	-	Mit	FABO/MTOR
Electron transfer flavoprotein beta subunit (ETFB)	92090596	-	-	0.82	0.00	0.78	0.00	1.22	0.00	-	-	Mit	FABO/ERBB2, MTOR
Methionine adenosyltransferase 1A (MAT1A)	81902386	-	-	0.63	0.00	1.14	0.01	2.99	0.00	0.40	0.00	C	MC/SREBF1
Aminoadipate-semialdehyde synthase (AASS)	46395955	-	-	0.70	0.00	-	-	2.80	0.00	0.43	0.00	C	LysD/CREB
3-Hydroxyisobutyrate dehydrogenase (HIBADH)	32363159	-	-	0.85	0.01	-	-	2.30	0.01	-	-	C	VC/MYC, FOXO4
Serine dehydratase (SDS)	52783414	-	-	-	-	-	-	2.09	0.02	0.05	0.01	C	CM/FOXA2
Chitinase-like 3 (Chil3)	51315803	2.52	0.01	0.41	0.01	-	-	3.59	0.00	-	-	C	CM/IL4
Keratin 18 (KRT18)	148886614	-	-	-	-	1.34	0.00	2.55	0.00	1.49	0.00	C	IFO, A(−)/TGFB1
Keratin 8 (KRT8)	90110028	-	-	-	-	1.33	0.00	2.60	0.00	1.44	0.00	C	IFO, A(−)/TGFB1
Vitronectin (VTN)	1722806	-	-	-	-	9.54	0.02	-	-	-	-	ES	CMA/FXR, LXR
Serum amyloid A1 (SAA1)	134159	-	-	1.20	0.04	30.47	0.00	-	-	-	-	ES	APR/FXR, LXR
Prohibitin 1 (PHB1)	54038835	-	-	0.81	0.02	-	-	1.47	0.01	-	-	Mit	TR, MitO/IL6, MYC
Histidine triad nucleotide-binding protein 1 (HINT1)	2495231	-	-	-	-	-	-	1.29	0.05	-	-	N	TR, PurC/TGFB1
Calreticulin (CALR)	117502	0.91	0.01	-	-	-	-	1.22	0.01	-	-	EPR	TR, CP(+)/Ca2+
Calnexin (CANX)	543921	0.88	0.03	-	-	-	-	1.40	0.00	-	-	EPR	PF/MYC, EGF
Cathepsin D (CTSD)	115718	-	-	-	-	1.30	0.01	2.37	0.00	-	-	L	Pro/TGFB1
Nipsnap homolog 1 (C. elegans) (NIPSNAP1)	17380130	-	-	-	-	-	-	1.44	0.01	-	-	Mit	NB/FOS, YY1
Progesterone receptor membrane comp. 1 (PGRMC1)	46577676	-	-	1.39	0.03	1.43	0.00	2.61	0.01	-	-	PM	SB/MTOR, TGFB1
Receptor accessory protein 6 (REEP6)	81881956	-	-	-	-	-	-	1.71	0.04	0.65	0.03	PM	ITR/RET

C: cytoplasm; EPR, endoplasmic reticulum; ES: extracellular space; L, lysosome; M, mitochondria; N: nucleus; PM: plasma membrane; A(−): negative regulation of apoptosis; AFO: actin filament organization; AM: amine metabolism; APR: acute phase response; ChM: cholesterol metabolism; CIIH: cellular iron ion homeostasis; CM: carbohydrate metabolism; CMA: cell-matrix adhesion: CRH: cell-redox homeostasis: CP(+): positive regulation of cell proliferation; CR(−): negative regulation of coagulation; GABAM: GABA metabolism; GlyM: glycine metabolism; GM: glutathione metabolism; ITR: intracellular transport regulation; FABO: fatty acid beta oxidation; FAM: fatty acid metabolism; IFO: intermediate filament organization; LC: lipid catabolism; LysD: lysine degradation; M: metabolism; MC: methionine catabolism; MCF: mitochondria cristae formation; MitO: mitochondrial organization; NB: neurotransmitter binding; NM: nucleotide metabolism; Pro: proteolysis; PurC: purine ribonucleotide catabolism; SB: steroid binding; SM: steroid metabolism; TCA: TCA cycle; TgM: triglyceride metabolism; TR: transcription regulation; TyrM: tyrosine metabolism; VC: valine catabolism; XM: xenobiotic metabolism; UC: urea cycle; “-”: protein expression is not changed; “0.000, .”