LETTER TO JMG

Naturally occurring mutations and functional polymorphisms in multidrug resistance 1 gene: correlation with microsatellite instability and lymphoid infiltration in colorectal cancers

U Potonik¹, M Ravnik-Glava^1,2, R Golouh³, D Glava¹

¹ Laboratory of Molecular Genetics, Institute of Pathology, Medical Faculty, Ljubljana, Slovenia
² Institute of Biochemistry, Medical Faculty, Ljubljana, Slovenia
³ Department of Pathology, Institute of Oncology, Ljubljana, Slovenia

Correspondence to:
Correspondence to:
Dr D Glava, University of Ljubljana, Medical Faculty, Institute of Pathology, Laboratory of Molecular Genetics, Korytkova 2, 1000 Ljubljana, Slovenia;
damjan.glavac@mf.uni-lj.si

Keywords: colorectal cancer; P glycoprotein function; MDR1 mutations; microsatellite instability

Abbreviations: Pgp, P glycoprotein; CRC, colorectal cancer; CIN, chromosome instability; HNPCC, hereditary non-polyposis colorectal cancer; MSI, microsatellite instability; MMR, mismatch repair; MSS, microsatellite stable; SSCA, single strand conformation analysis; HA heteroduplex analysis; DSCA, double strand conformation analysis

Pglycoprotein (Pgp), encoded by the MDR1 gene, is a transmembrane transporter that acts as an efflux pump in an ATP dependent fashion.¹ Multidrug resistance, the main problem in efficient cancer chemotherapy, is mainly caused by increased expression and acquired mutations in the MDR1 gene.² Pgp is expressed physiologically in epithelial cells of the kidney, liver, pancreas, and colon, suggesting its role in secretion of toxic compounds.³ Pgp is also expressed in the blood-brain barrier, adrenal glands, and lymphocytes where its role is still uncertain. Recently, additional functions for Pgp, including immune response⁴ and regulation of apoptosis,⁵ have been suggested in normal tissues and in cancers. High expression of Pgp at the apical surface of differentiated tubular structures was identified in previously untreated colorectal cancers (CRC)⁶ and its high expression at the leading edge of a colorectal carcinoma was associated with tumour progression.⁷

In contrast to the majority of CRC, which . . . [Full text of this article]

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