Expression of CYP3A4 in human breast tumour and non-tumour tissues
Cytochrome P450 3A4 (CYP3A4), a member of multigene superfamily of enzymes, plays a major role in the activation of procarcinogens such as polycyclic hydrocarbon dihydrodiols, aflatoxins and heterocyclic amines as well as of several drugs including tamoxifen which is used in breast cancer therapy. U...
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| Veröffentlicht in: | Cancer letters 2003-12, Vol.202 (1), p.17-23 |
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| creator | Kapucuoglu, Nilgün Coban, Tulay Raunio, Hannu Pelkonen, Olavi Edwards, Robert J. Boobis, Alan R. Iscan, Mumtaz |
| description | Cytochrome P450 3A4 (CYP3A4), a member of multigene superfamily of enzymes, plays a major role in the activation of procarcinogens such as polycyclic hydrocarbon dihydrodiols, aflatoxins and heterocyclic amines as well as of several drugs including tamoxifen which is used in breast cancer therapy. Using immunohistochemistry, the cellular distribution and the level of expression of CYP3A4 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP3A4 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 68% (17/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP3A4 was detected in normal epithelium and myoepithelium. Only focal staining was noted in some of the non-epithelial cells (e.g. endothelial cells) in normal breast tissues. When CYP3A4 staining was assessed semiquantitatively the mean staining score values of CYP3A4 were found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP3A4 protein is expressed in both tumour and normal breast tissue with an increased expression in tumours. |
| doi_str_mv | 10.1016/j.canlet.2003.08.015 |
| format | Article |
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Using immunohistochemistry, the cellular distribution and the level of expression of CYP3A4 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP3A4 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 68% (17/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP3A4 was detected in normal epithelium and myoepithelium. Only focal staining was noted in some of the non-epithelial cells (e.g. endothelial cells) in normal breast tissues. When CYP3A4 staining was assessed semiquantitatively the mean staining score values of CYP3A4 were found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP3A4 protein is expressed in both tumour and normal breast tissue with an increased expression in tumours.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2003.08.015</identifier><identifier>PMID: 14643022</identifier><identifier>CODEN: CALEDQ</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Adult ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Breast - enzymology ; Breast cancer ; Breast Neoplasms - enzymology ; Breast Neoplasms - pathology ; Breast tumour ; Cancer therapies ; Carcinoma, Ductal, Breast - enzymology ; Carcinoma, Ductal, Breast - pathology ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System - metabolism ; Cytochrome P4503A4 ; Estrogen receptor status ; Female ; Humans ; Immunoenzyme Techniques ; Immunohistochemistry ; Medical sciences ; Menopausal status ; Menopause ; Middle Aged ; Pharmacology. Drug treatments ; Polycyclic aromatic hydrocarbons ; Proteins ; Receptors, Estrogen - metabolism ; Smoking ; Tumors</subject><ispartof>Cancer letters, 2003-12, Vol.202 (1), p.17-23</ispartof><rights>2003 Elsevier Ireland Ltd</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Elsevier Limited Dec 8, 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-ce74c1953ff85ace963b1eaff54b33d38f3f11fea9ea930f7e0defad4d9bd2233</citedby><cites>FETCH-LOGICAL-c416t-ce74c1953ff85ace963b1eaff54b33d38f3f11fea9ea930f7e0defad4d9bd2233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304383503005445$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15307170$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14643022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kapucuoglu, Nilgün</creatorcontrib><creatorcontrib>Coban, Tulay</creatorcontrib><creatorcontrib>Raunio, Hannu</creatorcontrib><creatorcontrib>Pelkonen, Olavi</creatorcontrib><creatorcontrib>Edwards, Robert J.</creatorcontrib><creatorcontrib>Boobis, Alan R.</creatorcontrib><creatorcontrib>Iscan, Mumtaz</creatorcontrib><title>Expression of CYP3A4 in human breast tumour and non-tumour tissues</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Cytochrome P450 3A4 (CYP3A4), a member of multigene superfamily of enzymes, plays a major role in the activation of procarcinogens such as polycyclic hydrocarbon dihydrodiols, aflatoxins and heterocyclic amines as well as of several drugs including tamoxifen which is used in breast cancer therapy. Using immunohistochemistry, the cellular distribution and the level of expression of CYP3A4 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP3A4 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 68% (17/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP3A4 was detected in normal epithelium and myoepithelium. Only focal staining was noted in some of the non-epithelial cells (e.g. endothelial cells) in normal breast tissues. When CYP3A4 staining was assessed semiquantitatively the mean staining score values of CYP3A4 were found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP3A4 protein is expressed in both tumour and normal breast tissue with an increased expression in tumours.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Breast - enzymology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - enzymology</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast tumour</subject><subject>Cancer therapies</subject><subject>Carcinoma, Ductal, Breast - enzymology</subject><subject>Carcinoma, Ductal, Breast - pathology</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Cytochrome P4503A4</subject><subject>Estrogen receptor status</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Menopausal status</subject><subject>Menopause</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Polycyclic aromatic hydrocarbons</subject><subject>Proteins</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Smoking</subject><subject>Tumors</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2LFDEQhoMo7uzoPxBpEL11W-lK-uMirMOuCgt60IOnkE4qmKE7PSbdov_eDNOw4EEoKAqeqnp5GHvBoeLAm7fHyugw0lLVAFhBVwGXj9iOd21dtn0Hj9kOEESJHcordp3SEQCkaOVTdsVFIxDqesfe3_4-RUrJz6GYXXH4_gVvROFD8WOddCiGSDotxbJO8xoLHWwR5lBu4-JTWik9Y0-cHhM93_qefbu7_Xr4WN5__vDpcHNfGsGbpTTUCsN7ic51UhvqGxw4aeekGBAtdg4d5450nwvBtQSWnLbC9oOta8Q9e3O5e4rzz_x3UZNPhsZRB5rXpFouakDsM_jqH_CY44acTXEJEhvZZHDPxIUycU4pklOn6Ccd_ygO6mxYHdXFsDobVtCpbDivvdyOr8NE9mFpU5qB1xugk9GjizoYnx44idDy9vz_3YWj7OyXp6iS8RQMWR_JLMrO_v9J_gJti5qr</recordid><startdate>20031208</startdate><enddate>20031208</enddate><creator>Kapucuoglu, Nilgün</creator><creator>Coban, Tulay</creator><creator>Raunio, Hannu</creator><creator>Pelkonen, Olavi</creator><creator>Edwards, Robert J.</creator><creator>Boobis, Alan R.</creator><creator>Iscan, Mumtaz</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20031208</creationdate><title>Expression of CYP3A4 in human breast tumour and non-tumour tissues</title><author>Kapucuoglu, Nilgün ; Coban, Tulay ; Raunio, Hannu ; Pelkonen, Olavi ; Edwards, Robert J. ; Boobis, Alan R. ; Iscan, Mumtaz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-ce74c1953ff85ace963b1eaff54b33d38f3f11fea9ea930f7e0defad4d9bd2233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Breast - enzymology</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - enzymology</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast tumour</topic><topic>Cancer therapies</topic><topic>Carcinoma, Ductal, Breast - enzymology</topic><topic>Carcinoma, Ductal, Breast - pathology</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Cytochrome P4503A4</topic><topic>Estrogen receptor status</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Menopausal status</topic><topic>Menopause</topic><topic>Middle Aged</topic><topic>Pharmacology. 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Using immunohistochemistry, the cellular distribution and the level of expression of CYP3A4 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP3A4 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 68% (17/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP3A4 was detected in normal epithelium and myoepithelium. Only focal staining was noted in some of the non-epithelial cells (e.g. endothelial cells) in normal breast tissues. When CYP3A4 staining was assessed semiquantitatively the mean staining score values of CYP3A4 were found to be significantly higher in tumours compared to that of normal breast tissues. 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| ispartof | Cancer letters, 2003-12, Vol.202 (1), p.17-23 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Aged Antineoplastic agents Biological and medical sciences Breast - enzymology Breast cancer Breast Neoplasms - enzymology Breast Neoplasms - pathology Breast tumour Cancer therapies Carcinoma, Ductal, Breast - enzymology Carcinoma, Ductal, Breast - pathology Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - metabolism Cytochrome P4503A4 Estrogen receptor status Female Humans Immunoenzyme Techniques Immunohistochemistry Medical sciences Menopausal status Menopause Middle Aged Pharmacology. Drug treatments Polycyclic aromatic hydrocarbons Proteins Receptors, Estrogen - metabolism Smoking Tumors |
| title | Expression of CYP3A4 in human breast tumour and non-tumour tissues |
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