Methylation profile of the promoter CpG islands of 14 “drug-resistance” genes in hepatocellular carcinoma

Table 2 The “drug resistance” genes in this study

Resistance mechanism	Genes and ref.	Function
Plasma membrane	ABCG2	Belongs to the abc transporter family, appears to play a major role in the multidrug resistance
transporters/pump		phenotype of MCF-7 breast cancer cell line. When over-expressed, the transfected cells become
decrease or increase to		resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular
concentration		accumulation reduce intracellular drug of daunorubicin, and manifest an
		ATP-dependent increase in the efflux of rhodamine
	CFTR	Belongs to the abc transporter family. MRP subfamily, involved in the transport of chloride ions
	RALBP1	Activates specifically hydrolysis of GTP bound to RAC1 and CDC42. Mediates ATP-dependent
		transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin(DOX) and is the major
		ATP-dependent transporter of glutathioneconjugates of electrophiles (GS-E) and DOX in
		erythrocytes. Can catalyze transport of glutathione conjugates and xenobiotics, and may
		contribute to the multidrug resistance phenomenon
Transcription factor	ATF2	Belongs to the bZIP family, ATF subfamily, binding the cAMP response element (CRE)
and/or tumor suppressor		(consensus sequence: 5’GTGACGT(A/C)(A/G)-3') as a transcription activator
	TP53	Acts as a tumor suppressor in many tumor types, involved in cell cycle regulation
		as a transcription activator that acts to negatively regulate cell division by controlling
		a set of genes required for this process
The enzymes involved in	CAT	Belonging to the catalase family ,serves to protect cells from the toxic effects of
drug activation or inactivation		hydrogen peroxide
metabolism abnormality	GSTP1	Belongs to the GST superfamily. Pi family; Conjugation of reduced glutathione to
		a wide number of exogenous and endogenous hydrophobic electrophiles
	TOP2B	Control of topological states of DNA by ATP-dependent breakage, passage and
		rejoining of double-stranded DNA
	DCK	Required for the phosphorylation of several deoxyribonucleosides and certain
		nucleoside analogs widely employed as antiviral and chemotherapeutic agents
Cell signaling alteration and	RAF1	Belongs to the Ser/Thr family of protein kinases. RAF subfamily. Involved in
cell cycle checkpoints alteration		the transduction of mitogenic signals from the cell membrane to the nucleus as a
		part of the Ras-dependent signaling pathway from receptors to the nucleus
	SKP2	Involved in regulation of G1/S transition as substrate recognition component of the
		SCF (SKP1-CUL1-F- box protein) E3 ubiquitin ligase complex which mediates the
		ubiquitination and subsequent proteasomal degradation of target proteins involved in
		cell cycle progression, signal transduction and transcription
Unclear mechanisms	B2M	Beta-2-microglobulin is the beta-chain of major histocompatibility complex class I
		molecules, Containing 1 immunoglobulin-like domain
	OCLN	May play a role in the formation and regulation of the tight junction (TJ)
		paracellular permeability barrier
	SPF45	Involved in nuclear mRNA splicing, via spliceosome

Note: All the information in this table was obtained from the web site of the OMIM section of the locus link (http://www.ncbi.nlm. nih.gov/LocusLink/) and GeneCards(http://bioinfo.weizmann.ac.il/cards/).