Developmental Regulation and Induction of Cytochrome P450 2W1, an Enzyme Expressed in Colon Tumors

• DOI: 10.1371/journal.pone.0122820
• Publication Date: 2015-04-06T13:38:41Z
• Authors: Eva Choong; Jia Guo; Anna Persson; Susanne Virding; Inger Johansson; Souren Mkrtchian; Magnus Ingelman-S...
• Keywords: 0301 basic medicine; Science; Q; R; Gene Expression Regulation, Developmental; Antineoplastic Agents; Hep G2 Cells; Epigenesis, Genetic; 3. Good health; Gastrointestinal Tract; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Cytochrome P-450 Enzyme System; Cell Line, Tumor; Imatinib Mesylate; Medicine; Animals; Humans; Colorectal Neoplasms; Cytochrome P450 Family 2; Research Article

Cytochrome P450 2W1 (CYP2W1) is expressed predominantly in colorectal and also hepatic tumors, whereas the levels are insignificant corresponding normal human adult tissues. CYP2W1 has been proposed as an attractive target for cancer (CRC) therapy by exploiting its ability to activate duocarmycin prodrugs cytotoxic metabolites. However, endogenous function, regulation developmental pattern of expression remain unexplored. Here we report murine gastrointestinal The gene colon small intestine commence at early stages embryonic life completely silenced shortly after birth. Immunohistochemical analysis fetal revealed that restricted crypt cells. silencing birth correlates with increased methylation CpG-rich regions both genes. Analysis adenocarcinoma cell line HCC2998 can be induced e.g. antitumor agent imatinib, linoleic acid derivatives. imatinib mediated induction suggests adjuvant treatment duocarmycins thus would involve tumor followed activated prodrugs. Taken together these data strongly support further exploration a specific drug CRC.