Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases

Smith, Gillian; Wolf, C. Roland; Deeni, Yusuf Y.; Dawe, Robert; Evans, Alan; Comrie, M.; Ferguson, J.; Ibbotson, S.H.

doi:10.1016/s0140-6736(03)13081-4

Cited by 133 publications

(155 citation statements)

References 30 publications

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“…These findings were consistent with the recently described association between CYP3A4 and nodal metastases (6). Of these enzymes, CYP2S1 and 26A1 are linked to retinoid metabolism (7,8), and 4V2 has been linked to myristic acid -hydroxylase activity (9). CYP3A4 is the only enzyme of this group potentially linked to the metabolism of AA to (Ϯ)-5,6-, (Ϯ)-8,9-, (Ϯ)-11,12-, and (Ϯ)-14,15-EET regioisomers, based on a preliminary report (10).…”

supporting

confidence: 93%

“…After transfection of MCF7 cells, 120 clones were isolated by ring cloning under G418 selection and analyzed by quantitative PCR for CYP3A4 expression levels. Two clones, one expressing sequence III (supplemental Table S1) (clone [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and the other sequence IV (supplemental Table S1) (clone [4][5][6][7][8][9][10][11][12][13][14] showing greater than 70% reductions in CYP3A4 mRNA expression by real time PCR and Western analysis, were selected for our studies. Six nontarget clones, NT-1 to NT-6 were isolated using the manufacturer's recommended nontarget sequence (SABiosciences, Frederick, MD).…”

Section: -(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium Bromidementioning

confidence: 99%

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CYP3A4 Mediates Growth of Estrogen Receptor-positive Breast Cancer Cells in Part by Inducing Nuclear Translocation of Phospho-Stat3 through Biosynthesis of (±)-14,15-Epoxyeicosatrienoic Acid (EET)

Mitra

Guo

Milani

et al. 2011

Journal of Biological Chemistry

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supporting

confidence: 93%

Section: -(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium Bromidementioning

confidence: 99%

CYP3A4 Mediates Growth of Estrogen Receptor-positive Breast Cancer Cells in Part by Inducing Nuclear Translocation of Phospho-Stat3 through Biosynthesis of (±)-14,15-Epoxyeicosatrienoic Acid (EET)

Mitra

Guo

Milani

et al. 2011

Journal of Biological Chemistry

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“…All other dioxininducible P450s are members of the CYP1 family and this suggests that CYP2S1 may have similar functional characteristics and metabolic substrates as CYP1 P450s (31,32). The immunohistochemical localization of CYP2S1 protein in normal colon is a novel finding although a high level of CYP2S1 mRNA has previously been identified by real-time quantitative PCR in this tissue (33). CYP2S1 was localized to both epithelial cells and chronic inflammatory cells present in the lamina propria.…”

Section: Discussionmentioning

confidence: 79%

Cytochrome P450 Profile of Colorectal Cancer: Identification of Markers of Prognosis

Kumarakulasingham

Rooney

Dundas

et al. 2005

Clinical Cancer Research

152

143

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Purpose: The cytochromes P450 (P450) are a multigene family of enzymes with a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs, carcinogens, and endogenous compounds. The purpose of this study was to define the P450 profile of colorectal cancer and establish the prognostic significance of expression of individual P450s in colorectal cancer. Experimental Design: Immunohistochemistry for a panel of 23 P450s was done on a colorectal cancer tissue microarray consisting of 264 primary colorectal cancers, 91lymph node metastasis, and 10 normal colorectal samples. The intensity of immunoreactivity in each sample was established by light microscopy. Results: The most frequently expressed form of P450 in normal colon was CYP3A4. In primary colorectal cancer, several P450s (CYP1B1, CYP2S1, CYP2U1, CYP3A5, and CYP51) were present at a significantly higher level of intensity compared with normal colon. P450 expression was also detected in lymph node metastasis and the presence of several P450s (CYP1B1, CYP2A/2B, CYP2F1, CYP4V2, and CYP39) in the lymph node metastasis strongly correlated with their presence in corresponding primary tumors. The presence of strong CYP51 (log-rank = 12.11, P = 0.0005) or strong CYP2S1 (log-rank = 6.72, P = 0.0095) immunoreactivity were associated with poor prognosis. CYP51 was also an independent marker of prognosis (P = 0.009). Conclusions: The expression of individual P450s has been established in colorectal cancer. Several P450s show increased expression in colorectal cancer. High expression of CYP51or CYP2S1 were associated with poor prognosis and CYP51is an independent marker of prognosis.

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“…Section 1734 solely to indicate this fact. 6 The abbreviations used are: RACE, rapid amplification of cDNA ends; AHR, aryl hydrocarbon receptor; ARNT, aryl hydrocarbon receptor nuclear translocator; XRE, xenobiotic-responsive element; HIF-1, hypoxia-inducible factor-1; HRE, hypoxia response element; EMSA, electrophoretic mobility shift assay; CREB, cAMP-responsive element-binding protein. …”

mentioning

confidence: 99%

“…Families 1-4 are often also inducible by xenobiotics. Members of family 1 are inducible by the potent tumor promoter, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), 6 and carcinogenic polycyclic aromatic hydrocarbons via the aryl hydrocarbon receptor (AHR) (2). Rylander et al (3) identified human CYP2S1 by performing a homology search in a sequence data base, whereas we cloned mouse Cyp2s1 as a dioxin-inducible transcript in the mouse hepatoma cell line, Hepa-1, in which cells it is maximally induced about 10-fold (4).…”

mentioning

confidence: 99%

A Novel Promoter Element Containing Multiple Overlapping Xenobiotic and Hypoxia Response Elements Mediates Induction of Cytochrome P4502S1 by Both Dioxin and Hypoxia

Rivera¹,

Wang²,

Saarikoski

et al. 2007

Journal of Biological Chemistry

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Cytochrome P4502S1 (CYP2S1) is expressed at high levels in epithelial tissues and is inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) via the aryl hydrocarbon receptor (AHR). Transcriptional initiation of mouse Cyp2s1 was found to occur at three regions, ϳ198, 102, and 22 nucleotides from the translational initiation codon. Approximately 400 nucleotides upstream of its translational initiation codon, mouse Cyp2s1 contains three overlapping xenobiotic-responsive element (XRE) sequences, which make a major contribution toward dioxin inducibility. Each XRE sequence in this trimeric XRE can bind the AHR/aryl hydrocarbon receptor nuclear translocator (ARNT) dimer in a dioxin-dependent fashion in vitro and can mediate dioxin-dependent transcription. Cyp2s1 is also markedly inducible by hypoxia. Induction is dependent on hypoxiainducible factor-1 (HIF-1) and is mediated in large part by three overlapping hypoxia response elements (HREs) embedded within the trimeric XRE segment. Although each HRE within this segment can bind HIF-1␣/ARNT in vitro, the most 3 HRE contributes the most toward hypoxia inducibility. AHR/ARNT and HIF-1␣/ARNT dimers bind to the region containing the trimeric XRE segment of the endogenous Cyp2s1 gene in vivo in a dioxin-dependent fashion and hypoxia-dependent fashion, respectively. These observations identify a novel regulatory cassette that mediates changes in Cyp2s1 expression.The cytochrome P450 superfamily consists of at least 57 genes in humans and 102 genes in mice (1). In general, mammalian cytochrome P450s in families 1-4 metabolize foreign compounds (xenobiotics), although they also frequently metabolize endogenous molecules, such as steroids and fatty acids. Families 1-4 are often also inducible by xenobiotics. Members of family 1 are inducible by the potent tumor promoter, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), 6 and carcinogenic polycyclic aromatic hydrocarbons via the aryl hydrocarbon receptor (AHR) (2). Rylander et al. (3) identified human CYP2S1 by performing a homology search in a sequence data base, whereas we cloned mouse Cyp2s1 as a dioxin-inducible transcript in the mouse hepatoma cell line, Hepa-1, in which cells it is maximally induced about 10-fold (4). CYP2S1 is unusual for a non-CYP1 family member in being inducible by dioxin (although another Cyp2 family member, Cyp2a5, has recently been shown also to be dioxin-inducible (5)). Human CYP2S1 has also been shown to be inducible in skin by coal tar, which contains high concentrations of polycyclic aromatic hydrocarbon ligands for AHR. Human CYP2S1 can convert alltrans-retinoic acid to the catabolic products, 4-hydroxyretinoic acid and 5,6-epoxyretinoic acid (6), and it has been reported that the enzyme can metabolize naphthalene to two products (7). Both mouse and human CYP2S1 are expressed robustly in most epithelial surfaces and tissues, including the lung and intestinal tract and at all stages of embryogenesis (3, 8 -10).The facts that all other previously well characterized dioxininducible cytochrome P45...

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Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases

Cited by 133 publications

References 30 publications

CYP3A4 Mediates Growth of Estrogen Receptor-positive Breast Cancer Cells in Part by Inducing Nuclear Translocation of Phospho-Stat3 through Biosynthesis of (±)-14,15-Epoxyeicosatrienoic Acid (EET)

CYP3A4 Mediates Growth of Estrogen Receptor-positive Breast Cancer Cells in Part by Inducing Nuclear Translocation of Phospho-Stat3 through Biosynthesis of (±)-14,15-Epoxyeicosatrienoic Acid (EET)

Cytochrome P450 Profile of Colorectal Cancer: Identification of Markers of Prognosis

A Novel Promoter Element Containing Multiple Overlapping Xenobiotic and Hypoxia Response Elements Mediates Induction of Cytochrome P4502S1 by Both Dioxin and Hypoxia

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