Expression of cytochrome P450 CYP1B1 in breast cancer

McKay, Judith; Melvin, William T.; Ah‐See, A. K.; Ewen, S. W. B.; Greenlee, William F.; Marcus, Carol S.; Burke, Mary; Murray, Graeme I.

doi:10.1016/0014-5793(95)01126-y

Cited by 114 publications

(69 citation statements)

References 20 publications

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“…Higher levels are found in a wide range of human cancers including cancers of the skin, brain, testis (85) and breast (86). CYP1B1 converts oestrogen to 4-hydroxylated metabolites (87) that may initiate breast cancer in humans (88). The enzyme also plays an important role in activating diverse procarcinogens including PAHs, aryl and heterocyclic amines and nitroarenes to reactive metabolites that cause DNA damage (Table 1) (89,90).…”

Section: Cyp1b1mentioning

confidence: 99%

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Božina¹,

Bradamante

Lovrić

2009

Archives of Industrial Hygiene and Toxicology

165

111

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The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities of multiple genes, while single genes have a limited impact on cancer risk. Multigenic approach in addition to environmental determinants in large sample studies is crucial for a reliable evaluation of any moderate gene effect. This article brings a review of current knowledge on the relations between the polymorphisms of some CYPs and drug activity/toxicity and cancer risk.

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Section: Cyp1b1mentioning

confidence: 99%

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Božina¹,

Bradamante

Lovrić

2009

Archives of Industrial Hygiene and Toxicology

165

111

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“…COMT has a higher affinity for 2-OHE 2 over 4-OHE 2 , resulting in an increased genotoxicity of the 4-OHE 2 metabolite (Tsuchiya et al 2005). High concentrations of 4-OHE 2 metabolites have been associated with human breast cancers (Rogan et al 2003), and elevated CYP1B1 mRNA transcripts have been identified in many cancerous tissues including breast, testis, and ovary (McKay et al 1995, Murray et al 1997 suggesting that elevated levels of CYP1B1-mediated E 2 metabolism can lead to carcinogenesis. 2-OHE 2 metabolites appear to be tumor inhibitors (Tsuchiya et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Scornaienchi

Thornton²,

Willett³

et al. 2010

Journal of Endocrinology

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Cytochrome P4501 (CYP1) and CYP3A proteins are primarily responsible for the metabolism of 17b-estradiol (E 2 ) in mammals. We have cloned and heterologously expressed CYP1A, CYP1B1, CYP1C1, CYP1C2, CYP1D1, and CYP3A65 from zebrafish (Danio rerio) to determine the CYP-mediated metabolism of E 2 in a non-mammalian species. Constructs of each CYP cDNA were created using a leader sequence from the bacterial ompA gene to allow appropriate expression in Escherichia coli without 5 0 modification of the gene. Membrane vesicles were purified, and functional CYP protein was verified using carbon monoxide difference spectra and fluorescent catalytic assays with the substrates 7-ethoxyresorufin and 7-benzyloxy-4-(trifluoromethyl)-coumarin. Rates of in vitro E 2 metabolism into 4-hydroxyE 2 (4-OHE 2 ), 2-hydroxyE 2 (2-OHE 2 ), and 16a-hydroxyE 1 (16a-OHE 1 ) metabolites were determined by gas chromatography/mass spectrometry. The 2-OHE 2 metabolite was produced by all CYPs tested, while 4-OHE 2 was only detected following incubation with CYP1A, CYP1B1, CYP1C1, and CYP1C2. The 16a-OHE 1 metabolite was only produced by CYP1A. The highest rates of E 2 metabolism were from CYP1A and CYP1C1, followed by CYP1C2. CYP1B1, CYP1D1, and CYP3A65 had low rates of E 2 metabolism. E 2 metabolism by zebrafish CYP1A, CYP1C1, and CYP1C2 produced similar ratios of 4-OHE 2 to 2-OHE 2 as previous studies with mammalian CYP1As. CYP1B1 formed the highest ratio of 4-OHE 2 to 2-OHE 2 metabolites. Contrary to mammals, these results suggest that fish CYP1A and CYP1C proteins are primarily responsible for E 2 metabolism, with only minor contributions from CYP3A65 and CYP1B1. Similar to mammals, 2-OHE 2 is the predominant metabolite from CYP-mediated E 2 metabolism in fish, suggesting that all vertebrate species produce the same major E 2 metabolite.

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“…Although CYP1B1 expression has been observed in multiple cancers examined to date (colon, lung, renal, bladder, and glaucoma), it shows particularly high expression in many of the hormone-mediated cancers (prostate, breast, endometrial, and ovarian; refs. 5,11,12). CYP1B1 is also implicated in the etiology of hormone-mediated tumors, as it is responsible for hormone metabolism and the formation of toxic metabolites from both endogenous and exogenous molecules (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics and Regulation of Human CytochromeP450 1B1: Implications in Hormone-Mediated Tumor Metabolism and a Novel Target for Therapeutic Intervention

Sissung

Price

Sparreboom

et al. 2006

Molecular Cancer Research

135

128

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Several of the hormone-mediated cancers (breast, endometrial, ovarian, and prostate) represent major cancers in both incidence and mortality rates. The etiology of these cancers is in large part modulated by the hormones estrogen and testosterone. As advanced disease develops, the common treatment for these cancers is chemotherapy. Thus, genes that can alter tissue response to hormones and alter clinical response to chemotherapy are of major interest. The cytochrome P450 1B1 (CYP1B1) may be involved in disease progression and modulate the treatment in the above hormone-mediated cancers. This review will focus on the pharmacogenetics of CYP1B1 in relation to hormone-mediated cancers and provide an assessment of cancer risk based on CYP1B1 polymorphisms and expression. In addition, it will provide a summary of CYP1B1 gene regulation and expression in normal and neoplastic tissue. (Mol Cancer Res 2006;4(3):135 -50)

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Expression of cytochrome P450 CYP1B1 in breast cancer

Cited by 114 publications

References 20 publications

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Pharmacogenetics and Regulation of Human CytochromeP450 1B1: Implications in Hormone-Mediated Tumor Metabolism and a Novel Target for Therapeutic Intervention

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