Skip to main content
Top
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha

Authors: Isabel Conde, María VT Lobo, Javier Zamora, Julio Pérez, Francisco J González, Emilio Alba, Benito Fraile, Ricardo Paniagua, María I Arenas

Published in: BMC Cancer | Issue 1/2008

Login to get access

Abstract

Background

The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P-450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to determine whether their expression profile in localized infiltrative breast cancer is associated with an increased risk of recurrent disease.

Methods

Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis.

Results

Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha.

Conclusion

Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator.
Appendix
Available only for authorised users
Literature
1.
go back to reference Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA: The nuclear receptor PXR is a lithocholic acids sensor that protects against liver toxicity. Proc Natl Acad Sci USA. 2001, 98: 3369-3374. 10.1073/pnas.051551698.CrossRefPubMedPubMedCentral Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA: The nuclear receptor PXR is a lithocholic acids sensor that protects against liver toxicity. Proc Natl Acad Sci USA. 2001, 98: 3369-3374. 10.1073/pnas.051551698.CrossRefPubMedPubMedCentral
2.
go back to reference Gardner-Stephen D, Heydel JM, Goyal A, Lu Y, Xie W, Lindblom T, Mackenzie P, Radominska-Pandya A: Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression. Drug Metabolism Disposition. 2004, 32: 340-347. 10.1124/dmd.32.3.340.CrossRefPubMedPubMedCentral Gardner-Stephen D, Heydel JM, Goyal A, Lu Y, Xie W, Lindblom T, Mackenzie P, Radominska-Pandya A: Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression. Drug Metabolism Disposition. 2004, 32: 340-347. 10.1124/dmd.32.3.340.CrossRefPubMedPubMedCentral
3.
go back to reference Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterstrom RH, Perlmann T, Lehmann JM: An orphan nuclear receptor activated by pregnanes defines a novel steroid-signaling pathway. Cell. 1998, 92: 73-82. 10.1016/S0092-8674(00)80900-9.CrossRefPubMed Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterstrom RH, Perlmann T, Lehmann JM: An orphan nuclear receptor activated by pregnanes defines a novel steroid-signaling pathway. Cell. 1998, 92: 73-82. 10.1016/S0092-8674(00)80900-9.CrossRefPubMed
4.
go back to reference Mangelsdorf DJ, Evans RM: The RXR heterodimers and orphan receptors. Cell. 1995, 83: 841-850. 10.1016/0092-8674(95)90200-7.CrossRefPubMed Mangelsdorf DJ, Evans RM: The RXR heterodimers and orphan receptors. Cell. 1995, 83: 841-850. 10.1016/0092-8674(95)90200-7.CrossRefPubMed
5.
go back to reference Lehmann JM, Mc Knee DD, Watson MA, Willson TM, Moore JT, Kliewer SA: The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998, 102: 1016-1023. 10.1172/JCI3703.CrossRefPubMedPubMedCentral Lehmann JM, Mc Knee DD, Watson MA, Willson TM, Moore JT, Kliewer SA: The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998, 102: 1016-1023. 10.1172/JCI3703.CrossRefPubMedPubMedCentral
6.
go back to reference Blumberg B, Sabbagh WJr, Juguilon H, Bolado JJr, Van Meter CM, Ong ES, Evans RM: SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 1998, 12: 3195-3205. 10.1101/gad.12.20.3195.CrossRefPubMedPubMedCentral Blumberg B, Sabbagh WJr, Juguilon H, Bolado JJr, Van Meter CM, Ong ES, Evans RM: SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 1998, 12: 3195-3205. 10.1101/gad.12.20.3195.CrossRefPubMedPubMedCentral
7.
go back to reference Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Wrighton SA, Hancock M, Kim RB, Strom S, Thummel K, Russell CG, Hudson JR, Schuetz EG, Boguski MS: The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics. 2001, 11: 555-572. 10.1097/00008571-200110000-00003.CrossRefPubMed Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Wrighton SA, Hancock M, Kim RB, Strom S, Thummel K, Russell CG, Hudson JR, Schuetz EG, Boguski MS: The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics. 2001, 11: 555-572. 10.1097/00008571-200110000-00003.CrossRefPubMed
8.
go back to reference Gonzalez FJ, Liu SY, Yano M: Regulation of cytochrome P450 genes: molecular mechanisms. Pharmacogenetics. 1993, 3: 51-57. 10.1097/00008571-199302000-00006.CrossRefPubMed Gonzalez FJ, Liu SY, Yano M: Regulation of cytochrome P450 genes: molecular mechanisms. Pharmacogenetics. 1993, 3: 51-57. 10.1097/00008571-199302000-00006.CrossRefPubMed
9.
go back to reference Zhang H, LeCluyse E, Liu L, Hu M, Matoney L, Zhu W, Yan B: Rat pregnane X receptor: molecular cloning, tissue distribution and xenobiotic regulation. Arch Biochem Biophys. 1999, 368: 14-22. 10.1006/abbi.1999.1307.CrossRefPubMed Zhang H, LeCluyse E, Liu L, Hu M, Matoney L, Zhu W, Yan B: Rat pregnane X receptor: molecular cloning, tissue distribution and xenobiotic regulation. Arch Biochem Biophys. 1999, 368: 14-22. 10.1006/abbi.1999.1307.CrossRefPubMed
10.
go back to reference Savas U, Wester MR, Griffin KJ, Johnson EF: Rabbit pregnane X receptor is activated by rifampicin. Drug Metab Dispos. 2000, 28: 529-537.PubMed Savas U, Wester MR, Griffin KJ, Johnson EF: Rabbit pregnane X receptor is activated by rifampicin. Drug Metab Dispos. 2000, 28: 529-537.PubMed
11.
go back to reference LeCluyse EL: Pregnane X receptor: molecular basis for species differences in CYP3A induction by xenobiotics. Chem-Biol Inter. 2001, 134: 283-289. 10.1016/S0009-2797(01)00163-6.CrossRef LeCluyse EL: Pregnane X receptor: molecular basis for species differences in CYP3A induction by xenobiotics. Chem-Biol Inter. 2001, 134: 283-289. 10.1016/S0009-2797(01)00163-6.CrossRef
12.
go back to reference El-Rayes BF, Ali S, Heilbrun LK, Lababidi S, Bouwman D, Visscher D, Philip PA: Cytochrome P450 and glutathione transferase expression in human breast cancer. Clin Cancer Res. 2003, 9: 1705-1709.PubMed El-Rayes BF, Ali S, Heilbrun LK, Lababidi S, Bouwman D, Visscher D, Philip PA: Cytochrome P450 and glutathione transferase expression in human breast cancer. Clin Cancer Res. 2003, 9: 1705-1709.PubMed
13.
go back to reference Kapucuoglu N, Coban T, Raunio H, Pelkonen O, Edwards RJ, Boobis AR, Iscan M: Expression of CYP3A4 in human breast tumor and non-tumor tissues. Cancer Lett. 2003, 202: 17-23. 10.1016/j.canlet.2003.08.015.CrossRefPubMed Kapucuoglu N, Coban T, Raunio H, Pelkonen O, Edwards RJ, Boobis AR, Iscan M: Expression of CYP3A4 in human breast tumor and non-tumor tissues. Cancer Lett. 2003, 202: 17-23. 10.1016/j.canlet.2003.08.015.CrossRefPubMed
14.
go back to reference Dotzlaw H, Leygue E, Watson , Murphy LC: The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin Cancer Res. 1999, 5: 2103-2107.PubMed Dotzlaw H, Leygue E, Watson , Murphy LC: The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin Cancer Res. 1999, 5: 2103-2107.PubMed
15.
go back to reference Miki Y, Suzuki T, Kitada K, Yabuki N, Shibuya R, Moriya T, Ishida T, Ohuchi N, Blumberg B, Sasano H: Expression of the Steroid and Xenobiotic Receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma. Cancer Res. 2006, 66: 535-542. 10.1158/0008-5472.CAN-05-1070.CrossRefPubMed Miki Y, Suzuki T, Kitada K, Yabuki N, Shibuya R, Moriya T, Ishida T, Ohuchi N, Blumberg B, Sasano H: Expression of the Steroid and Xenobiotic Receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma. Cancer Res. 2006, 66: 535-542. 10.1158/0008-5472.CAN-05-1070.CrossRefPubMed
16.
go back to reference Hellmold H, Rylander T, Magnusson M, Reihner E, Warner M, Gustafsson JA: Characterization of cytochrome P450 enzymes in human breast tissue from reduction mammaplasties. J Clin Endocrinol Metab. 1998, 83: 886-895. 10.1210/jc.83.3.886.PubMed Hellmold H, Rylander T, Magnusson M, Reihner E, Warner M, Gustafsson JA: Characterization of cytochrome P450 enzymes in human breast tissue from reduction mammaplasties. J Clin Endocrinol Metab. 1998, 83: 886-895. 10.1210/jc.83.3.886.PubMed
17.
go back to reference Bieche I, Girault I, Urbain E, Tozlu S, Lidereau R: Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma. Breast Cancer Res. 2004, 6: 252-263. 10.1186/bcr784.CrossRef Bieche I, Girault I, Urbain E, Tozlu S, Lidereau R: Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma. Breast Cancer Res. 2004, 6: 252-263. 10.1186/bcr784.CrossRef
18.
go back to reference Huang Z, Fasco M, Figge H, Keyomarsi K, Kaminsky L: Expression of cytochromes P450 in human breast tissue and tumors. Drug Metab Dispos. 1996, 24 (8): 899-905.PubMed Huang Z, Fasco M, Figge H, Keyomarsi K, Kaminsky L: Expression of cytochromes P450 in human breast tissue and tumors. Drug Metab Dispos. 1996, 24 (8): 899-905.PubMed
19.
go back to reference Fukuen S, Fukuda T, Matsuda H, Sumida A, Yamamoto I, Inaba T, Azuma J: Identification of the novel splicing variants for the hPXR in human livers. Biochem Biophys Res Commun. 2002, 298: 433-438. 10.1016/S0006-291X(02)02469-5.CrossRefPubMed Fukuen S, Fukuda T, Matsuda H, Sumida A, Yamamoto I, Inaba T, Azuma J: Identification of the novel splicing variants for the hPXR in human livers. Biochem Biophys Res Commun. 2002, 298: 433-438. 10.1016/S0006-291X(02)02469-5.CrossRefPubMed
20.
go back to reference Lamba V, Yasuda K, Lamba JK, Assem M, Davila J, Strom S, Schuetz EG: PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators. Toxicol Appl Pharmacol. 2004, 199: 251-265. 10.1016/j.taap.2003.12.027.CrossRefPubMed Lamba V, Yasuda K, Lamba JK, Assem M, Davila J, Strom S, Schuetz EG: PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators. Toxicol Appl Pharmacol. 2004, 199: 251-265. 10.1016/j.taap.2003.12.027.CrossRefPubMed
21.
go back to reference Ravdin PM, Green S, Dorr TM, McGuire WL, Fabian C, Pugh RP, Carter RD, Rivkin SE, Borst JR, Belt RJ, Metch B, Osborne CK: Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. J Clin Oncol. 1992, 10: 1284-1291.PubMed Ravdin PM, Green S, Dorr TM, McGuire WL, Fabian C, Pugh RP, Carter RD, Rivkin SE, Borst JR, Belt RJ, Metch B, Osborne CK: Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. J Clin Oncol. 1992, 10: 1284-1291.PubMed
22.
go back to reference Cai Y, Konishi T, Han G, Campwala KW, French SW, Wan Y-JY: The role of hepatocyte RXR-α in xenobiotic-sensing nuclear receptor-mediated pathways. Eur J Pharm Sci. 2002, 15: 89-96. 10.1016/S0928-0987(01)00211-1.CrossRefPubMed Cai Y, Konishi T, Han G, Campwala KW, French SW, Wan Y-JY: The role of hepatocyte RXR-α in xenobiotic-sensing nuclear receptor-mediated pathways. Eur J Pharm Sci. 2002, 15: 89-96. 10.1016/S0928-0987(01)00211-1.CrossRefPubMed
23.
go back to reference Masuyama H, Hiramatsu Y, Kodama J-I, Kudo T: Expression and potential roles of pregnane X receptor in endometrial cancer. J Clin Endocrinol Metab. 2003, 88: 4446-4454. 10.1210/jc.2003-030203.CrossRefPubMed Masuyama H, Hiramatsu Y, Kodama J-I, Kudo T: Expression and potential roles of pregnane X receptor in endometrial cancer. J Clin Endocrinol Metab. 2003, 88: 4446-4454. 10.1210/jc.2003-030203.CrossRefPubMed
24.
go back to reference Squires EJ, Sueyoshi T, Negishi M: Cytoplasmic localization of Pregnane X Receptor and ligand-dependent nuclear translocation in mouse liver. J Biol Chem. 2004, 279: 49307-49314. 10.1074/jbc.M407281200.CrossRefPubMed Squires EJ, Sueyoshi T, Negishi M: Cytoplasmic localization of Pregnane X Receptor and ligand-dependent nuclear translocation in mouse liver. J Biol Chem. 2004, 279: 49307-49314. 10.1074/jbc.M407281200.CrossRefPubMed
25.
go back to reference Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM: Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature (Lond). 1992, 355: 446-449. 10.1038/355446a0.CrossRef Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM: Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature (Lond). 1992, 355: 446-449. 10.1038/355446a0.CrossRef
26.
go back to reference Kliewer SA, Umesono K, Noonan DJ, Heyman RA, Evans RM: Convergene of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimers formation of their receptors. Nature (Lond). 1992, 358: 771-774. 10.1038/358771a0.CrossRef Kliewer SA, Umesono K, Noonan DJ, Heyman RA, Evans RM: Convergene of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimers formation of their receptors. Nature (Lond). 1992, 358: 771-774. 10.1038/358771a0.CrossRef
27.
go back to reference Lawrence JA, Merino MJ, Simpson JF, Manrow RE, Page DL, Steeg PS: A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor. Cancer Epidemiol Biomarkers Prev. 1998, 7: 29-35.PubMed Lawrence JA, Merino MJ, Simpson JF, Manrow RE, Page DL, Steeg PS: A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor. Cancer Epidemiol Biomarkers Prev. 1998, 7: 29-35.PubMed
28.
go back to reference Ariga N, Moriya T, Suzuki T, Kimura M, Ohuchi N, Sasano H: Retinoic acid receptor and retinoid X receptor in ductal carcinoma in situ and intraductal proliferative lesions of the human breast. Jpn J Cancer Res. 2000, 91: 1169-1176.CrossRefPubMed Ariga N, Moriya T, Suzuki T, Kimura M, Ohuchi N, Sasano H: Retinoic acid receptor and retinoid X receptor in ductal carcinoma in situ and intraductal proliferative lesions of the human breast. Jpn J Cancer Res. 2000, 91: 1169-1176.CrossRefPubMed
29.
go back to reference Suzuki T, Moriya T, Sugawara A, Ariga N, Takabayashi H, Sasano H: Retinoid receptors in human breast carcinoma: possible modulators of in situ estrogen metabolism. Breast Cancer Res Treat. 2001, 65: 31-40. 10.1023/A:1006433929792.CrossRefPubMed Suzuki T, Moriya T, Sugawara A, Ariga N, Takabayashi H, Sasano H: Retinoid receptors in human breast carcinoma: possible modulators of in situ estrogen metabolism. Breast Cancer Res Treat. 2001, 65: 31-40. 10.1023/A:1006433929792.CrossRefPubMed
30.
go back to reference Pratt WB, Toft DO: Steroid receptor interactions with heat shock proteins and immunophilin chaperones. Endocr Rev. 1997, 18: 306-360. 10.1210/er.18.3.306.PubMed Pratt WB, Toft DO: Steroid receptor interactions with heat shock proteins and immunophilin chaperones. Endocr Rev. 1997, 18: 306-360. 10.1210/er.18.3.306.PubMed
31.
go back to reference Zhan S-K, Lehmann J, Hoffmann B, Dawson MI, Cameron J, Graupner G, Hhermann T, Tran P, and Pfahl M: Homodimer formation of retinoid X receptor induced by 9-cis- retinoic acid. Nature (Lond). 1992, 358: 587-591. 10.1038/358587a0.CrossRef Zhan S-K, Lehmann J, Hoffmann B, Dawson MI, Cameron J, Graupner G, Hhermann T, Tran P, and Pfahl M: Homodimer formation of retinoid X receptor induced by 9-cis- retinoic acid. Nature (Lond). 1992, 358: 587-591. 10.1038/358587a0.CrossRef
32.
go back to reference Crowe DL, Chandraratna AS: A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands. Breast Cancer Res. 2004, 6: R546-R555. 10.1186/bcr913.CrossRefPubMedPubMedCentral Crowe DL, Chandraratna AS: A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands. Breast Cancer Res. 2004, 6: R546-R555. 10.1186/bcr913.CrossRefPubMedPubMedCentral
33.
go back to reference Baum M, Houghton J, Riley D: Tamoxifen to prevent breast cancer. Lancet. 1991, 338: 114-10.1016/0140-6736(91)90104-W.CrossRefPubMed Baum M, Houghton J, Riley D: Tamoxifen to prevent breast cancer. Lancet. 1991, 338: 114-10.1016/0140-6736(91)90104-W.CrossRefPubMed
34.
go back to reference Dorssers LC, Flier Van der S, Brinkman A, van Agthoven T, Veldscholte J, Bems EM, Klijn JG, Beex LV, Foekens JA: Tamoxifen resistance in breast cancer: elucidating mechanisms. Drugs. 2001, 61: 1721-1733. 10.2165/00003495-200161120-00004.CrossRefPubMed Dorssers LC, Flier Van der S, Brinkman A, van Agthoven T, Veldscholte J, Bems EM, Klijn JG, Beex LV, Foekens JA: Tamoxifen resistance in breast cancer: elucidating mechanisms. Drugs. 2001, 61: 1721-1733. 10.2165/00003495-200161120-00004.CrossRefPubMed
35.
go back to reference Clemons M, Danson S, Howell A: Tamoxifen ('Nolvadex'): a review. Cancer Treat Rev. 2002, 28: 165-180. 10.1016/S0305-7372(02)00036-1.CrossRefPubMed Clemons M, Danson S, Howell A: Tamoxifen ('Nolvadex'): a review. Cancer Treat Rev. 2002, 28: 165-180. 10.1016/S0305-7372(02)00036-1.CrossRefPubMed
36.
go back to reference Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002, 30: 869-874. 10.1124/dmd.30.8.869.CrossRefPubMed Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002, 30: 869-874. 10.1124/dmd.30.8.869.CrossRefPubMed
37.
go back to reference Desai PB, Nallani SC, Sane RS, Moore LB, Goodwin BJ, Buckley DJ, Buckley AR: Induction of cytochrome P450 3A4 in primary human hepatocytes and activation of the human pregnane X receptor by tamoxifen and 4-hydroxytamoxifen. Drug Metab Dispos. 2002, 30: 608-612. 10.1124/dmd.30.5.608.CrossRefPubMed Desai PB, Nallani SC, Sane RS, Moore LB, Goodwin BJ, Buckley DJ, Buckley AR: Induction of cytochrome P450 3A4 in primary human hepatocytes and activation of the human pregnane X receptor by tamoxifen and 4-hydroxytamoxifen. Drug Metab Dispos. 2002, 30: 608-612. 10.1124/dmd.30.5.608.CrossRefPubMed
38.
go back to reference Iscan M, Klaavuniemi T, Coban T, Kapucuoglu N, Pelkonen O, Raunio H: The expression of cytochrome P450 enzymes in human breast tumors and normal breast tissue. Breast Cancer Res Treat. 2001, 70: 47-54. 10.1023/A:1012526406741.CrossRefPubMed Iscan M, Klaavuniemi T, Coban T, Kapucuoglu N, Pelkonen O, Raunio H: The expression of cytochrome P450 enzymes in human breast tumors and normal breast tissue. Breast Cancer Res Treat. 2001, 70: 47-54. 10.1023/A:1012526406741.CrossRefPubMed
39.
go back to reference Modugno F, Knoll C, Kanbour-Shakir A, Romkes M: A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003, 82: 191-197. 10.1023/B:BREA.0000004376.21491.44.CrossRefPubMed Modugno F, Knoll C, Kanbour-Shakir A, Romkes M: A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003, 82: 191-197. 10.1023/B:BREA.0000004376.21491.44.CrossRefPubMed
40.
go back to reference Sane RS, Buckley DJ, Buckley AR, Nallani SC, Desai PB: Role of human Pregnane X Receptor in tamoxifen and 4-hydroxytamoxifen mediated CYP3A4 induction in primary human hepatocytes and LS174T cells. Drug Metab Dispos. 2008 February 25 Sane RS, Buckley DJ, Buckley AR, Nallani SC, Desai PB: Role of human Pregnane X Receptor in tamoxifen and 4-hydroxytamoxifen mediated CYP3A4 induction in primary human hepatocytes and LS174T cells. Drug Metab Dispos. 2008 February 25
41.
go back to reference Synold TW, Dussault I, Forman BM: The orphan nuclear receptor SXR co-ordinately regulates drug metabolism and efflux. Nature Med. 2001, 7: 584-590. 10.1038/87912.CrossRefPubMed Synold TW, Dussault I, Forman BM: The orphan nuclear receptor SXR co-ordinately regulates drug metabolism and efflux. Nature Med. 2001, 7: 584-590. 10.1038/87912.CrossRefPubMed
Metadata
Title
Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha
Authors
Isabel Conde
María VT Lobo
Javier Zamora
Julio Pérez
Francisco J González
Emilio Alba
Benito Fraile
Ricardo Paniagua
María I Arenas
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-174

Other articles of this Issue 1/2008

BMC Cancer 1/2008 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine