Expression of cytochrome P450IA in breast cancer

Murray, G. I.; Co, Foster; Ts, Barnes; Rj, Weaver; Sw, Ewen; Melvin, William T.; Burke,

doi:10.1038/bjc.1991.222

Cited by 31 publications

(21 citation statements)

References 16 publications

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“…The data presented here demonstrate that human breast and colon tumours constitutively express low levels of certain cytochrome P450 isozymes. This is in agreement with previous findings which demonstrate that P450 expression is detectable in tumour biopsy samples from these tissues (Senler et al, 1985;Forrester et al, 1990;Murray et al, 1991). The constitutive expression of a protein in the CYP2A gene family in both the breast and colon samples is interesting in view of the recent report of the isolation of a CYP2A protein from mouse liver tumours (Maurice et al, 1991).…”

Section: Controlsupporting

confidence: 81%

Regulation of cytochrome P450 gene expression in human colon and breast tumour xenografts

Smith

Harrison²,

East³

et al. 1993

Br J Cancer

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The cytochrome P450-dependent monooxygenases (P450s) are thought to have evolved as a protective adaptive response against the toxic effects of environmental chemicals (Nebert & Gonzalez, 1987;Wolf, 1991). This polymorphic multigene superfamily of hemoproteins can metabolise a vast number of lipophilic exogenous compounds, including drugs and environmental toxins (Guengerich, 1987;Conney, 1982), to products which can be more readily excreted. Ironically, in addition to their role in detoxification, P450 enzymes also play a central role in the conversion of chemical toxins and procarcinogens to their ultimately toxic or carcinogenic forms (see Nebert & Gonzalez, 1987;Wolf, 1991). The ability of P450s to activate chemical toxins has been exploited in cancer chemotherapy, where a variety of anticancer drugs require metabolic activation in order to exert their cytotoxic effects (Powis & Prough, 1987). Understanding the genetic and environmental factors which regulate human cytochrome P450 expression is therefore of central importance. For a variety of reasons, at present there is very little precise information available on the regulation of these genes in man, particularly in extra-hepatic tissues.Animal models have been widely used to study drug metabolising enzymes and the factors which regulate their expression. Although these have provided extremely valuable information, their use is inherently limited by the extent to which they represent the human system. For example, there are significant species and strain differences in the expression and regulation of drug metabolising enzymes (Omenn & Gelboin, 1984). Indeed, compounds which are potent regulators of these enzymes in one species can have greatly reduced or no effects in another (Poland et al., 1980). This, together with genetic considerations, implies that no animal model can truly represent the enzyme systems found in man (Miles et al., 1990).In vitro studies of human P450 gene regulation are difficult as the expression, and ability to regulate the levels of most of these proteins by foreign compounds is lost in both primary hepatocytes and tumour cell lines in culture (Paine, 1990). This is a particular problem for studying the effects of hormonal and other metabolic factors on P450 gene expression , 1986;Stanley et al., 1992). In view of these limitations, we have tested a model in which human gene regulation by both endogenous and exogenous modulators can be studied in vivo. In this system, human tumours are grown as xenografts in immune deficient mice. This model, which has been widely used to evaluate the response of human tumours to anticancer drugs, is taken as an accurate representation of the behaviour of these compounds in human tumour tissues (Berger et al., 1991). We describe the use of this system to study the effects of a range of compounds, known to modulate P450 expression in experimental animals, on human tumour P450 levels. The compounds chosen included agents which exhibit profound species differences in their inductive effects in exp...

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Section: Controlsupporting

confidence: 81%

Regulation of cytochrome P450 gene expression in human colon and breast tumour xenografts

Smith

Harrison²,

East³

et al. 1993

Br J Cancer

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“…At low levels, estrogen is primarily metabolized by CYP3A4 (74). However, CYP3A4 is often not found expressed in estrogen-responsive tissues, such as breast, depending on the ethnicity of the population under investigation (75)(76)(77)(78). Furthermore, plasma and tissue levels of estrogen levels are not always concordant.…”

Section: Estrogen Metabolismmentioning

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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“…Recently, a new dioxin-inducible CYP1 P450 subfamily has been identified, containing one form to date, CYP1B1 [12]. Using immunohistochemistry, we have previously identified a CYPl-immunoreactive protein in breast cancer [13] and in this study we have investigated the expression of individual forms of the two known CYP1 gene subfamilies in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression of cytochrome P450 CYP1B1 in breast cancer

et al. 1995

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The expression of CYP1B1 has been identified in breast cancer using the reverse transcriptase-polymerase chain reaction and immunoblotting. CYP1B1 mRNA was expressed in the majority of breast tumours and immunoblotting of breast tumours identified a single protein band of molecular weight 60 kDa corresponding to the predicted molecular weight of human CYP1B1. This is the first study to identify CYP1B1 expression in a turnout where it may represent a previously unknown pathway for the metabolism of oestradiol and chemotherapeutic drugs.

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Expression of cytochrome P450IA in breast cancer

Abstract: Images Figure 1 Figure 2 Figure 3

Cited by 31 publications

References 16 publications

Regulation of cytochrome P450 gene expression in human colon and breast tumour xenografts

Regulation of cytochrome P450 gene expression in human colon and breast tumour xenografts

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

Expression of cytochrome P450 CYP1B1 in breast cancer

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