Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

Table 1 The ABCB1, ABCC2 and ABCG2 mRNA and protein levels in intestinal tissue from patients with ulcerative colitis

		Controls	Inactive disease				Active disease				Ref.
		Colon	Colon	P value	Rectum	P value	Colon	P value	Rectum	P value
Gene	ABCB11	1 (ref)	NA	NS	NA		22%	< 0.001	34%	< 0.01	[72]
	ABCC21	1 (ref)	NA	NS	NA		NA	NS	NA	NS	[72]
	ABCG21	1 (ref)	NA	NS	NA		11%	< 0.001	16%	< 0.001	[72]
Array	ABCB12	287	-1.5								[40]
	ABCC22	81	-8.6								[40]
Protein	ABCG23	100 (9/9)	80 (53/67)				24 (13/54)	0.01			[73]

¹The ABCB1, ABCC2 and ABCG2 mRNA levels in colon and rectum tissue from patients with ulcerative colitis in remission (n = 17) or with active disease (n = 16) compared to the levels in colon tissue from healthy controls (n = 17). mRNA levels are normalised to the villin mRNA level. P values compared to the expression in the controls;

²Microarray analyses of pooled cRNA from uninflamed colonic tissue from 4 patients with UC and 4 control subjects. Fold change expression in colon tissue compared to controls. Statistically significant expression levels of ABCB1 were found in UC patients compared to controls by RT-PCR analyses using 18S RNA as internal control (P < 0.05);

³Quantitative immunohistochemistry of formalin-fixed paraffin-embedded (FFPE) colonic biopsies from 9 healthy individuals and 36 patients with ulcerative colitis. The values are n % (samples with positive staining/total number). P value for active colitis compared to controls and inactive colitis, respectively. NA: Not available; NS: Not significant.

Table 2 The ABCB1, ABCC2 and ABCG2 mRNA levels in intestinal tissue from patients with adenomas and colorectal cancer and healthy individuals

	Unaffected tissue	P value1	Adenomas/carcinomas	P value1	P value2	Ref.
ABCB1						[13]
Healthy individuals	0.012 ± 0.008
Mild/moderate dysplasia cases	0.009 ± 0.004	NS	0.005 ± 0.004	< 0.050	< 0.001
Severe dysplasia cases	0.009 ± 0.030	NS	0.003 ± 0.002	< 0.050	< 0.001
Cancer patients	0.009 ± 0.014 (distant)	< 0.05	0.003 ± 0.005	< 0.001	< 0.001
	0.007 ± 0.009 (adjacent)	< 0.05			< 0.010
ABCC2						[14]
Healthy individuals	5.35 ± 3.24
Mild moderate dysplasia cases	4.62 ± 4.79	0.081	6.68 ± 6.77	0.87	0.037
Severe dysplasia cases	6.66 ± 8.47	0.880	10.18 ± 11.52	0.27	0.240
Cancer patients	28.06 ± 68.84 (distant)	0.036	87.50 ± 270.21	0.0046	0.0037
	11.44 ± 25.58 (adjacent)	0.690			< 0.0001
ABCG2						[14]
Healthy individuals	718.06 ± 761.24
Mild moderate dysplasia	732.85 ± 2305.28	0.550	56.02 ± 118.42	< 0.0001	< 0.0001
Severe dysplasia	448.02 ± 195.34	0.840	76.31 ± 102.63	< 0.0001	< 0.0001
Cancer patients	6679 ± 58353 (distant)	0.080	98.41 ± 476.36	< 0.0001	< 0.0001
	1302 ± 10090 (adjacent)	0.011			< 0.0001

¹P values for comparison of the expression levels in tissue from healthy individuals adjusted for age and gender. Samples were available for 18 healthy controls, 88-94 patients with mild/moderate dysplasia, 12 with severe dysplacia, and 121-122 patients with CRC;

²P value for the comparison of the expression levels in morphologically unaffected and affected tissue from the same individual using Paired Student’s t-test. All values are mean ± SD. ABCB1 mRNA levels are normalised to the β-actin mRNA level. ABCC2 and ABCG2 mRNA levels are normalised to 18S RNA levels. Matching samples were available from ABCG2: 66-75 cases with mild-moderate dysplasia, 11 cases with severe dysplasia, and 63-80 and 66-99 CRC cases (distant unaffected tissue, and adjacent unaffected tissue, respectively). NS: Not significant.