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Gene Review

CYP1B1  -  cytochrome P450, family 1, subfamily B,...

Homo sapiens

Synonyms: CP1B, CYPIB1, Cytochrome P450 1B1, GLC3A, P4501B1
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Disease relevance of CYP1B1


Psychiatry related information on CYP1B1


High impact information on CYP1B1

  • Tumors may be initiated by metabolic conversion of E2 to 4-hydroxyestradiol catalyzed by a specific 4-hydroxylase (CYP1B1) and by further activation of this catechol to reactive semiquinone/quinone intermediates [8].
  • Estradiol 4-hydroxylation appears to be a characteristic reaction catalyzed by human CYP1B1 [9].
  • We also propose that CYP1B1 may act as a modifier of MYOC expression and that these two genes may interact through a common pathway [10].
  • By a combination of single-strand conformation polymorphism and direct cycle sequencing, MYOC mutations were detected in 8 (13.3%) of the 60 individuals, CYP1B1 mutations were detected in 3 (5%) of the 60 individuals, and no PITX2 mutations were detected [10].
  • CYP1B1 mutations involved cases of juvenile open-angle glaucoma, as well as cases of congenital glaucoma [10].

Chemical compound and disease context of CYP1B1


Biological context of CYP1B1


Anatomical context of CYP1B1

  • These results show that xenoestrogens, by altering the ratio of CYP1B1/CYP1A1, could redirect estradiol metabolism in a more toxic pathway in the breast cell line MCF-7 [3].
  • The estradiol metabolites by CYP1B1 received particular attention because of their causative role in malignant transformation of endometrium [2].
  • In addition, an E229K CYP1B1 mutation was found in a woman with a germ line HNF1alpha mutation in a familial adenomatosis context [4].
  • Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells [16].
  • In contrast, differences between NOK and SVpgC2a, e.g., for CYP1B1, may reflect alteration caused by immortalization and aid identification of early stage tumor markers in oral epithelium [17].

Associations of CYP1B1 with chemical compounds


Enzymatic interactions of CYP1B1

  • We examined the substrate oxidation activities of recombinant human CYP1B1 in yeast microsomes and compared these activities with those catalyzed by reconstituted systems containing recombinant CYP1A1 and CYP1A2 which were isolated from membranes of Escherichia coli in which respective cDNAs have been expressed [21].

Regulatory relationships of CYP1B1

  • CONCLUSIONS: In the absence of exogenous AhR ligands (such as cigarette smoke components), AhR overexpression up-regulated the expression of CYP1B1 in the early stage of lung adenocarcinoma [15].
  • These results suggest that CYP1A1 and CYP1B1 are differentially regulated in human pulmonary epithelial cells and give the first indication of the induction of CYP3A5 by glucocorticoids in human lung cells [19].
  • Overall, our novel findings indicate the upregulation of CYP1B1 by ATRA in HL-60 human promyelocytic leukemic cells shown for the first time to express PXR but not CAR mRNA [22].
  • Because CYP1B1 is known to be involved in mammary estrogen metabolism, we investigated whether the estrogen receptor status is influenced by the CYP1B1 genotypes [1].
  • An AHH-1 TK+/- cell derivative was developed that stably expresses human cytochrome P4501B1 (CYP1B1) cDNA in an extrachromosomal vector which confers resistance to 1-histidinol and co-expresses NADPH cytochrome P450 oxidoreductase (OR) [23].

Other interactions of CYP1B1

  • In multivariate analyses, gender, tobacco smoke exposure, and other factors were associated with the level of expression of CYP1B1, GSTP1, and other transcripts on a gene-specific basis, but substantial interindividual variability in mRNA expression remained unexplained [24].
  • These forms were present also in the reduction samples, with CYP2E1 and CYP1B1 being detected in all samples [25].
  • We did not observe any effect modification by BMI, PMH use and cigarette smoking for the CYP1B1 and COMT genotypes [12].
  • Alternatively, the Val CYP1B1 or His SULT1A1 allele with modified ability to metabolize estrogens could increase the level of genotoxic catechol estrogen (i.e., 4-hydroxy-estradiol) among smokers [13].
  • Generally, induction of CYP1A1, CYP1A2, and CYP1B1 is considered cardiotoxic through generating reactive oxygen species (ROS), DNA adducts, and endogenous arachidonic acid metabolites [26].

Analytical, diagnostic and therapeutic context of CYP1B1


  1. Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid receptor status in breast cancer. Bailey, L.R., Roodi, N., Dupont, W.D., Parl, F.F. Cancer Res. (1998) [Pubmed]
  2. CYP1B1 gene polymorphisms have higher risk for endometrial cancer, and positive correlations with estrogen receptor alpha and estrogen receptor beta expressions. Sasaki, M., Tanaka, Y., Kaneuchi, M., Sakuragi, N., Dahiya, R. Cancer Res. (2003) [Pubmed]
  3. Differential regulation of cytochrome P450 1A1 and 1B1 by a combination of dioxin and pesticides in the breast tumor cell line MCF-7. Coumoul, X., Diry, M., Robillot, C., Barouki, R. Cancer Res. (2001) [Pubmed]
  4. Association of CYP1B1 germ line mutations with hepatocyte nuclear factor 1alpha-mutated hepatocellular adenoma. Jeannot, E., Poussin, K., Chiche, L., Bacq, Y., Sturm, N., Scoazec, J.Y., Buffet, C., Van Nhieu, J.T., Bellanné-Chantelot, C., de Toma, C., Laurent-Puig, P., Bioulac-Sage, P., Zucman-Rossi, J. Cancer Res. (2007) [Pubmed]
  5. Cytochrome P450 1B1 expression in glial cell tumors: an immunotherapeutic target. Barnett, J.A., Urbauer, D.L., Murray, G.I., Fuller, G.N., Heimberger, A.B. Clin. Cancer Res. (2007) [Pubmed]
  6. Polymorphisms in genes involved in estrogen and progesterone metabolism and mammographic density changes in women randomized to postmenopausal hormone therapy: results from a pilot study. Lord, S.J., Mack, W.J., Van Den Berg, D., Pike, M.C., Ingles, S.A., Haiman, C.A., Wang, W., Parisky, Y.R., Hodis, H.N., Ursin, G. Breast Cancer Res. (2005) [Pubmed]
  7. Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women. Lee, K.M., Abel, J., Ko, Y., Harth, V., Park, W.Y., Seo, J.S., Yoo, K.Y., Choi, J.Y., Shin, A., Ahn, S.H., Noh, D.Y., Hirvonen, A., Kang, D. Br. J. Cancer (2003) [Pubmed]
  8. Is estradiol a genotoxic mutagenic carcinogen? Liehr, J.G. Endocr. Rev. (2000) [Pubmed]
  9. Regulation, function, and tissue-specific expression of cytochrome P450 CYP1B1. Murray, G.I., Melvin, W.T., Greenlee, W.F., Burke, M.D. Annu. Rev. Pharmacol. Toxicol. (2001) [Pubmed]
  10. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Vincent, A.L., Billingsley, G., Buys, Y., Levin, A.V., Priston, M., Trope, G., Williams-Lyn, D., Héon, E. Am. J. Hum. Genet. (2002) [Pubmed]
  11. Cytochrome P450 1B1 is overexpressed and regulated by hypomethylation in prostate cancer. Tokizane, T., Shiina, H., Igawa, M., Enokida, H., Urakami, S., Kawakami, T., Ogishima, T., Okino, S.T., Li, L.C., Tanaka, Y., Nonomura, N., Okuyama, A., Dahiya, R. Clin. Cancer Res. (2005) [Pubmed]
  12. Cytochrome P450 1B1 and catechol-O-methyltransferase polymorphisms and endometrial cancer susceptibility. McGrath, M., Hankinson, S.E., Arbeitman, L., Colditz, G.A., Hunter, D.J., De Vivo, I. Carcinogenesis (2004) [Pubmed]
  13. Interactions between genetic polymorphism of cytochrome P450-1B1, sulfotransferase 1A1, catechol-o-methyltransferase and tobacco exposure in breast cancer risk. Saintot, M., Malaveille, C., Hautefeuille, A., Gerber, M. Int. J. Cancer (2003) [Pubmed]
  14. Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1. Dawling, S., Roodi, N., Parl, F.F. Cancer Res. (2003) [Pubmed]
  15. Requirement of Aryl Hydrocarbon Receptor Overexpression for CYP1B1 Up-Regulation and Cell Growth in Human Lung Adenocarcinomas. Chang, J.T., Chang, H., Chen, P.H., Lin, S.L., Lin, P. Clin. Cancer Res. (2007) [Pubmed]
  16. Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells. Spink, D.C., Spink, B.C., Cao, J.Q., DePasquale, J.A., Pentecost, B.T., Fasco, M.J., Li, Y., Sutter, T.R. Carcinogenesis (1998) [Pubmed]
  17. Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen-immortalized oral keratinocytes. Vondracek, M., Weaver, D.A., Sarang, Z., Hedberg, J.J., Willey, J.C., Wärngård, L., Grafström, R.C. Int. J. Cancer (2002) [Pubmed]
  18. The redox protein thioredoxin-1 regulates the constitutive and inducible expression of the estrogen metabolizing cytochromes P450 1B1 and 1A1 in MCF-7 human breast cancer cells. Husbeck, B., Powis, G. Carcinogenesis (2002) [Pubmed]
  19. Induction and regulation of xenobiotic-metabolizing cytochrome P450s in the human A549 lung adenocarcinoma cell line. Hukkanen, J., Lassila, A., Päivärinta, K., Valanne, S., Sarpo, S., Hakkola, J., Pelkonen, O., Raunio, H. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
  20. Increased expression of cytochrome p450 1A1 and 1B1 genes in anti-estrogen-resistant human breast cancer cell lines. Brockdorff, B.L., Skouv, J., Reiter, B.E., Lykkesfeldt, A.E. Int. J. Cancer (2000) [Pubmed]
  21. Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Shimada, T., Gillam, E.M., Sutter, T.R., Strickland, P.T., Guengerich, F.P., Yamazaki, H. Drug Metab. Dispos. (1997) [Pubmed]
  22. Transcript profiling of cytochrome P450 genes in HL-60 human leukemic cells: upregulation of CYP1B1 by all-trans-retinoic acid. Kawai, M., Chen, J., Cheung, C.Y., Chang, T.K. Mol. Cell. Biochem. (2003) [Pubmed]
  23. Development of a human lymphoblastoid cell line constitutively expressing human CYP1B1 cDNA: substrate specificity with model substrates and promutagens. Crespi, C.L., Penman, B.W., Steimel, D.T., Smith, T., Yang, C.S., Sutter, T.R. Mutagenesis (1997) [Pubmed]
  24. Gene-environment interaction signatures by quantitative mRNA profiling in exfoliated buccal mucosal cells. Spivack, S.D., Hurteau, G.J., Jain, R., Kumar, S.V., Aldous, K.M., Gierthy, J.F., Kaminsky, L.S. Cancer Res. (2004) [Pubmed]
  25. Characterization of cytochrome P450 enzymes in human breast tissue from reduction mammaplasties. Hellmold, H., Rylander, T., Magnusson, M., Reihnér, E., Warner, M., Gustafsson, J.A. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  26. The role of aryl hydrocarbon receptor in the pathogenesis of cardiovascular diseases. Korashy, H.M., El-Kadi, A.O. Drug Metab. Rev. (2006) [Pubmed]
  27. Failure of Ah receptor to mediate induction of cytochromes P450 in the CYP1 family in the human hepatoma line SK-Hep-1. Roberts, E.A., Harper, P.A., Wong, J.M., Wang, Y., Yang, S. Arch. Biochem. Biophys. (2000) [Pubmed]
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