Potter_1998_Cancer.Res_58_2646

Reference

Title : Isolation and partial characterization of a cDNA encoding a rabbit liver carboxylesterase that activates the prodrug irinotecan (CPT-11) - Potter_1998_Cancer.Res_58_2646
Author(s) : Potter PM , Pawlik CA , Morton CL , Naeve CW , Danks MK
Ref : Cancer Research , 58 :2646 , 1998
Abstract :

We have isolated a cDNA encoding a rabbit carboxylesterase (CE; EC 3.1.1.1) that converts the camptothecin-derived prodrug irinotecan (CPT-11) to the potent topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin. NH2-terminal amino acid sequencing of a purified rabbit CE allowed the design of redundant oligonucleotides to perform PCR from rabbit liver cDNA. DNA sequencing of the PCR product confirmed the identity of the clone, and after both 5' and 3' rapid amplification of cDNA ends, oligonucleotide primers were designed to amplify the entire cDNA. The 1698-bp open reading frame encoded a 565-amino acid protein containing the characteristic CE B-1 and B-2 motifs, a hydrophobic NH2-terminal leader sequence, and the COOH-terminal residues HIEL that are thought to be responsible for protein localization in the endoplasmic reticulum. Transient expression of the cDNA in COS-7 cells resulted in CE activity in cell extracts and increased the sensitivity of cells to CPT-11. Additionally, stable expression of the rabbit liver CE cDNA in the human glioma U-373 MG cell line resulted in a 56-fold decrease in the IC50 value for CPT-11, whereas the expression of a human alveolar macrophage cDNA encoding a highly homologous CE produced no change in drug sensitivity.

PubMedSearch : Potter_1998_Cancer.Res_58_2646
PubMedID: 9635592
Gene_locus related to this paper: rabit-1cxes

Related information

Inhibitor Irinotecan
Substrate Irinotecan    Irinotecan
Gene_locus Irinotecan    Irinotecan    rabit-1cxes

Citations formats

Potter PM, Pawlik CA, Morton CL, Naeve CW, Danks MK (1998)
Isolation and partial characterization of a cDNA encoding a rabbit liver carboxylesterase that activates the prodrug irinotecan (CPT-11)
Cancer Research 58 :2646

Potter PM, Pawlik CA, Morton CL, Naeve CW, Danks MK (1998)
Cancer Research 58 :2646