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Quantifiable mRNA transcripts for tamoxifen-metabolising enzymes in human endometrium.

Singh, Maneesh N. and Stringfellow, Helen F. and Walsh, Michael J. and Ashton, Kate M. and Paraskevaidis, Evangelos and Abdo, Khalil R. and Martin-Hirsch, Pierre L. and Phillips, David H. and Martin, Frank L. (2008) Quantifiable mRNA transcripts for tamoxifen-metabolising enzymes in human endometrium. Toxicology, 249 (1). pp. 85-90. ISSN 0300-483X

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Abstract

Tamoxifen has been used in the management of receptor-positive breast cancer for >20 years. Usage confers an elevated risk of developing endometrial carcinoma. Its mechanism of carcinogenicity remains unresolved with controversy as to whether or not this is mediated through a genotoxic mechanism. Usage is not only associated with an elevated occurrence of endometrioid endometrial carcinoma, but also type 2 and mixed epithelial-stromal tumours (MESTs) that have a poorer prognosis. Following hysterectomy, endometrial tissues (n = 18) classified as benign (n = 6), non-tamoxifen-associated carcinoma (n = 6) and tamoxifen-associated carcinoma (n = 6) were obtained; quantitative gene expression was performed. Employing real-time RT-PCR, the relative gene expressions of phase I/II metabolic enzymes CYP1A2, CYP1B1 and CYP3A4, cathechol-O-methyltransferase (COMT) and SULT2A1 were ascertained. Measurable mRNA transcripts, especially for those genes associated with tamoxifen bioactivation, were quantifiable in all the tissues examined. Whether this is evidence that generation of genotoxic tamoxifen metabolites may occur in human endometrial tissue remains to be ascertained.

Item Type: Article
Journal or Publication Title: Toxicology
Uncontrolled Keywords: CYP3A4 ; Endometrial carcinoma ; Genotoxic ; Selective oestrogen receptor modulator ; SULT2A1 ; Tamoxifen
Subjects: G Geography. Anthropology. Recreation > GE Environmental Sciences
Departments: Faculty of Science and Technology > Lancaster Environment Centre
Faculty of Health and Medicine
ID Code: 31365
Deposited By: Mr Richard Ingham
Deposited On: 13 Jan 2010 15:09
Refereed?: Yes
Published?: Published
Last Modified: 06 Sep 2013 19:51
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/31365

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