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British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Jul;85(2):242–246. doi: 10.1054/bjoc.2001.1907

Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer

M C E McFadyen 1, M E Cruickshank 2, I D Miller 1, H L McLeod 3,1, W T Melvin 4, N E Haites 3,4, D Parkin 2, G I Murray 1
PMCID: PMC2364045  PMID: 11461084

Abstract

Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P= 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: cytochrome P450, docetaxel, anti-cancer drug

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Selected References

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  1. Arts H. J., Katsaros D., de Vries E. G., Massobrio M., Genta F., Danese S., Arisio R., Scheper R. J., Kool M., Scheffer G. L. Drug resistance-associated markers P-glycoprotein, multidrug resistance-associated protein 1, multidrug resistance-associated protein 2, and lung resistance protein as prognostic factors in ovarian carcinoma. Clin Cancer Res. 1999 Oct;5(10):2798–2805. [PubMed] [Google Scholar]
  2. ESTEVES J., DA FONSECA A., ANTUNES M. M. Aspectos epidemiológicos da tinha em Portugal; distribuiço dos casos em funço da idade, sexo e tipo de parasitismo. Port Med. 1955 Feb;39(2):65–71. [PubMed] [Google Scholar]
  3. Gonzalez F. J., Gelboin H. V. Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab Rev. 1994;26(1-2):165–183. doi: 10.3109/03602539409029789. [DOI] [PubMed] [Google Scholar]
  4. Guengerich F. P., Shimada T. Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol. 1991 Jul-Aug;4(4):391–407. doi: 10.1021/tx00022a001. [DOI] [PubMed] [Google Scholar]
  5. Hayes C. L., Spink D. C., Spink B. C., Cao J. Q., Walker N. J., Sutter T. R. 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9776–9781. doi: 10.1073/pnas.93.18.9776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Iyer L., Ratain M. J. Pharmacogenetics and cancer chemotherapy. Eur J Cancer. 1998 Sep;34(10):1493–1499. doi: 10.1016/s0959-8049(98)00230-5. [DOI] [PubMed] [Google Scholar]
  7. Kivistö K. T., Kroemer H. K., Eichelbaum M. The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions. Br J Clin Pharmacol. 1995 Dec;40(6):523–530. doi: 10.1111/j.1365-2125.1995.tb05796.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kristensen G. B., Tropé C. Epithelial ovarian carcinoma. Lancet. 1997 Jan 11;349(9045):113–117. doi: 10.1016/S0140-6736(96)06071-0. [DOI] [PubMed] [Google Scholar]
  9. Le Blanc G. A., Waxman D. J. Interaction of anticancer drugs with hepatic monooxygenase enzymes. Drug Metab Rev. 1989;20(2-4):395–439. doi: 10.3109/03602538909103550. [DOI] [PubMed] [Google Scholar]
  10. Lorigan P. C., Crosby T., Coleman R. E. Current drug treatment guidelines for epithelial ovarian cancer. Drugs. 1996 Apr;51(4):571–584. doi: 10.2165/00003495-199651040-00005. [DOI] [PubMed] [Google Scholar]
  11. Marre F., Sanderink G. J., de Sousa G., Gaillard C., Martinet M., Rahmani R. Hepatic biotransformation of docetaxel (Taxotere) in vitro: involvement of the CYP3A subfamily in humans. Cancer Res. 1996 Mar 15;56(6):1296–1302. [PubMed] [Google Scholar]
  12. McFadyen M. C., Breeman S., Payne S., Stirk C., Miller I. D., Melvin W. T., Murray G. I. Immunohistochemical localization of cytochrome P450 CYP1B1 in breast cancer with monoclonal antibodies specific for CYP1B1. J Histochem Cytochem. 1999 Nov;47(11):1457–1464. doi: 10.1177/002215549904701111. [DOI] [PubMed] [Google Scholar]
  13. McFadyen M. C., McLeod H. L., Jackson F. C., Melvin W. T., Doehmer J., Murray G. I. Cytochrome P450 CYP1B1 protein expression: a novel mechanism of anticancer drug resistance. Biochem Pharmacol. 2001 Jul 15;62(2):207–212. doi: 10.1016/s0006-2952(01)00643-8. [DOI] [PubMed] [Google Scholar]
  14. McKay J. A., Douglas J. J., Ross V. G., Curran S., Ahmed F. Y., Loane J. F., Murray G. I., McLeod H. L. Expression of cell cycle control proteins in primary colorectal tumors does not always predict expression in lymph node metastases. Clin Cancer Res. 2000 Mar;6(3):1113–1118. [PubMed] [Google Scholar]
  15. McKay J. A., Murray G. I., Weaver R. J., Ewen S. W., Melvin W. T., Burke M. D. Xenobiotic metabolising enzyme expression in colonic neoplasia. Gut. 1993 Sep;34(9):1234–1239. doi: 10.1136/gut.34.9.1234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McLeod H. L., McKay J. A., Collie-Duguid E. S., Cassidy J. Therapeutic opportunities from tumour biology in metastatic colon cancer. Eur J Cancer. 2000 Aug;36(13 Spec No):1706–1712. doi: 10.1016/s0959-8049(00)00150-7. [DOI] [PubMed] [Google Scholar]
  17. Murray G. I., McKay J. A., Weaver R. J., Ewen S. W., Melvin W. T., Burke M. D. Cytochrome P450 expression is a common molecular event in soft tissue sarcomas. J Pathol. 1993 Sep;171(1):49–52. doi: 10.1002/path.1711710110. [DOI] [PubMed] [Google Scholar]
  18. Murray G. I., Melvin W. T., Greenlee W. F., Burke M. D. Regulation, function, and tissue-specific expression of cytochrome P450 CYP1B1. Annu Rev Pharmacol Toxicol. 2001;41:297–316. doi: 10.1146/annurev.pharmtox.41.1.297. [DOI] [PubMed] [Google Scholar]
  19. Murray G. I., Shaw D., Weaver R. J., McKay J. A., Ewen S. W., Melvin W. T., Burke M. D. Cytochrome P450 expression in oesophageal cancer. Gut. 1994 May;35(5):599–603. doi: 10.1136/gut.35.5.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Murray G. I., Taylor M. C., McFadyen M. C., McKay J. A., Greenlee W. F., Burke M. D., Melvin W. T. Tumor-specific expression of cytochrome P450 CYP1B1. Cancer Res. 1997 Jul 15;57(14):3026–3031. [PubMed] [Google Scholar]
  21. Murray G. I. The role of cytochrome P450 in tumour development and progression and its potential in therapy. J Pathol. 2000 Dec;192(4):419–426. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH750>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  22. Nelson D. R., Koymans L., Kamataki T., Stegeman J. J., Feyereisen R., Waxman D. J., Waterman M. R., Gotoh O., Coon M. J., Estabrook R. W. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics. 1996 Feb;6(1):1–42. doi: 10.1097/00008571-199602000-00002. [DOI] [PubMed] [Google Scholar]
  23. Qazi F., McGuire W. P. The treatment of epithelial ovarian cancer. CA Cancer J Clin. 1995 Mar-Apr;45(2):88–101. doi: 10.3322/canjclin.45.2.88. [DOI] [PubMed] [Google Scholar]
  24. Rochat B., Morsman J. M., Murray G. I., Figg W. D., McLeod H. L. Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537–541. [PubMed] [Google Scholar]
  25. Sonnichsen D. S., Relling M. V. Clinical pharmacokinetics of paclitaxel. Clin Pharmacokinet. 1994 Oct;27(4):256–269. doi: 10.2165/00003088-199427040-00002. [DOI] [PubMed] [Google Scholar]

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