Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-22T05:55:22.626Z Has data issue: false hasContentIssue false

Dietary soya isoflavones and breast carcinogenesis: a perspective from a cell-culture model

Published online by Cambridge University Press:  14 December 2007

Lai K. Leung*
Affiliation:
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin N. T., Hong Kong Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin N. T., Hong Kong
Yee Man Yuen
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin N. T., Hong Kong
Hau Yi Leung
Affiliation:
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin N. T., Hong Kong
Yun Wang
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin N. T., Hong Kong
*
*Corresponding author: Dr Lai K. Leung, fax +852 26037732, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Southeast Asian women have a lower incidence of breast cancer than their counterparts in the West. Epidemiological studies have indicated that soya consumption may be a contributing factor. Carcinogenesis is a process involving multiple stages. The present review attempts to fit the cellular mechanisms attributed to soya isoflavones into these different stages. Many cell-culture studies have reported the growth-inhibitory effect of soya isoflavones; however, with the non-physiological concentrations employed in these studies it would be difficult to explain the protection mechanisms observed in epidemiological studies. Our laboratory has previously found that genistein inhibits cytochrome P450 (CYP)1A1 and CYP1B1. The inhibition implies that soya consumption may have the potential to prevent chemical carcinogenesis. The preferential inhibition of CYP1B1 may also block the oestrogen-initiated carcinogenesis. The antagonism of oestrogen receptor (ER) binding can affect the cell-proliferative phase, which is likely to be important in the promotion stage of breast cancer. Since our laboratory and others have indicated that genistein at physiological concentrations has no effect on the downstream activities of ER binding, the antagonism of ER is not likely to be a contributing factor in the disease prevention. Moreover, soya isoflavones cannot inhibit aromatase (CYP19), which is the enzyme responsible for oestrogen synthesis. In the present review various cellular activities altered by soya isoflavones are discussed

Type
Research Article
Copyright
Copyright © The Authors 2005

References

Allred, CD, Allred, KF, Ju, YH, Clausen, LM, Doerge, DR, Schantz, SL, Korol, DL, Wallig, MA & Helferich, WG (2004) Dietary genistein results in larger MNU-induced, oestrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats. Carcinogenesis 25, 211218.CrossRefGoogle Scholar
Allred, DC & Mohsin, SK (2000) Biological features of premalignant disease in the human breast. Journal of Mammary Gland Biology and Neoplasia 5, 351364CrossRefGoogle ScholarPubMed
American Cancer Society (1993) Cancer Facts and Figures. Atlanta, GA: American Cancer Society.Google Scholar
An, J, Tzagarakis-Foster, C, Scharschmidt, TC, Lomri, N & Leitman, DC (2001) Oestrogen receptor beta-selective transcriptional activity and recruitment of coregulators by phyto-oestrogens. Journal of Biological Chemistry 276, 1780817814.CrossRefGoogle Scholar
Appelt, LC & Reicks, MM (1999) Soy induces phase II enzymes but does not inhibit dimethylbenz[a]anthracene-induced carcinogenesis in female rats. Journal of Nutrition 129, 18201826.CrossRefGoogle ScholarPubMed
Barkhem, T, Andersson-Ross, C, Hoglund, M & Nilsson, S (1997) Characterization of the “Oestrogenicity” of tamoxifen and raloxifene in HepG2 cells: regulation of gene expression from an ERE controlled reporter vector versus regulation of the endogenous SHBG and PS2 genes. Journal of Steroid Biochemistry and Molecular Biology 62, 5364.CrossRefGoogle Scholar
Batistuzzo de Medeiros, SR, Krey, G, Hihi, AK & Wahli, W (1997) Functional interactions between the estrogen receptor and the transcription activator Sp1 regulate the estrogen-dependent transcriptional activity of the vitellogenin A1 io promoter. Journal of Biological Chemistry 272, 1825018260.CrossRefGoogle ScholarPubMed
Breinholt, V & Larsen, JC (1998) Detection of weak oestrogenic flavonoids using a recombinant yeast strain and a modified MCF7 cell proliferation assay. Chemical Research in Toxicology 11, 622629.CrossRefGoogle Scholar
Buters, JT, Sakai, S, Richter, T, Pineau, T, Alexander, DL, Savas, U, Doehmer, J, Ward, JM, Jefcoate, CR & Gonzalez, FJ (1999) Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas. Proceedings of the National Academy of Sciences USA 96, 19771982.CrossRefGoogle ScholarPubMed
Chae, YH, Ho, DK, Cassady, JM, Cook, VM, Marcus, CB & Baird, WM (1992) Effects of synthetic and naturally occurring flavonoids on metabolic activation of benzo[a]pyrene in hamster embryo cell cultures. Chemico-biological Interactions 82, 181193.CrossRefGoogle Scholar
Chan, HY & Leung, LK (2003) A potential protective mechanism of soya isoflavones against 7,12-dimethylbenz[a]anthracene tumour initiation. British Journal of Nutrition 90, 457465.CrossRefGoogle Scholar
Chen, WF & Wong, MS (2004) Genistein enhances insulin-like growth factor signaling pathway in human breast cancer (MCF-7) cells. Journal of Clinical Endocrinology and Metabolism 89, 23512359.CrossRefGoogle ScholarPubMed
Colditz, GA (1999) Hormones and breast cancer: evidence and implications for consideration of risks and benefits of hormone replacement therapy. Journal of Women's Health 8, 347357.CrossRefGoogle ScholarPubMed
Constantinou, AI, Kamath, N & Murley, JS (1998) Genistein inactivates bcl-2, delays the G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells. European Journal of Cancer 34, 19271934.CrossRefGoogle ScholarPubMed
Constantinou, AI, Lantvit, D, Hawthorne, M, Xu, X, van Breemen, RB & Pezzuto, JM (2001) Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats. Nutrition and Cancer 41, 7581.CrossRefGoogle ScholarPubMed
Cuzick, J (2003) Aromatase inhibitors in prevention – data from the ATAC (arimidex, tamoxifen alone or in combination) trial and the design of IBIS-II (the second International Breast Cancer Intervention Study). Recent Results in Cancer Research 163, 96103, discussion 264–266.CrossRefGoogle ScholarPubMed
Day, JK, Besch-Williford, C, McMann, TR, Hufford, MG, Lubahn, DB & MacDonald, RS (2001) Dietary genistein increased DMBA-induced mammary adenocarcinoma in wild-type, but not ER alpha KO, mice. Nutrition and Cancer 39, 226232.CrossRefGoogle Scholar
Dechering, K, Boersma, C & Mosselman, S (2000) Oestrogen receptors alpha and beta: two receptors of a kind? Current Medicinal Chemistry 7, 561576.CrossRefGoogle ScholarPubMed
Dees, C, Foster, JS, Ahamed, S & Wimalasena, J (1997) Dietary oestrogens stimulate human breast cells to enter the cell cycle. Environmental Health Perspectives 105, Suppl. 3, 633636Google ScholarPubMed
Dertinger, SD, Lantum, HB, Silverstone, AE & Gasiewicz, TA (2000) Effect of 3′-methoxy-4′-nitroflavone on benzo[a]pyrene toxicity. Aryl hydrocarbon receptor-dependent and -independent mechanisms. Biochemical Pharmacology 60, 189196.CrossRefGoogle Scholar
Environmental Protection Agency (1990) Aerometric Information Retrieval System (AIRS), Data for 1985–1990. Washington, DC: Environmental Protection Agency and US Government Printing Office.Google Scholar
Fioravanti, L, Cappelletti, V, Miodini, P, Ronchi, E, Brivio, M & Di Fronzo, G (1998) Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro. Cancer Letters 130, 143152.CrossRefGoogle ScholarPubMed
Frey, RS & Singletary, KW (2003) Genistein activates p38 mitogen-activated protein kinase, inactivates ERK1/ERK2 and decreases Cdc25C expression in immortalized human mammary epithelial cells. Journal of Nutrition 133, 226231.CrossRefGoogle ScholarPubMed
Fuchs, SY, Adler, V, Pincus, MR & Ronai, Z (1998) MEKK1/JNK signaling stabilizes and activates p53. Proceedings of the National Academy of Sciences USA 95, 1054110546.CrossRefGoogle ScholarPubMed
Gallo, D, Giacomelli, S, Cantelmo, F, Zannoni, GF, Ferrandina, G, Fruscella, E, Riva, A, Morazzoni, P, Bombardelli, E, Mancuso, S & Scambia, G (2001) Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy. Breast Cancer Research and Treatment 69, 153164.CrossRefGoogle ScholarPubMed
Gross, A, McDonnell, JM & Korsmeyer, SJ (1999 a) BCL-2 family members and the mitochondria in apoptosis. Genes and Development 13, 18991911.CrossRefGoogle ScholarPubMed
Gross, A, Yin, XM, Wang, K, Wei, MC, Jockel, J, Milliman, C, Erdjument-Bromage, H, Tempst, P & Korsmeyer, SJ (1999 b) Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death. Journal of Biological Chemistry 274, 11561163.CrossRefGoogle Scholar
Hall, JM, Couse, JF & Korach, KS (2001) The multifaceted mechanisms of estradiol and oestrogen receptor signaling. Journal of Biological Chemistry 276, 3686936872.CrossRefGoogle ScholarPubMed
Harris, RM, Wood, DM, Bottomley, L, Blagg, S, Owen, K, Hughes, PJ, Waring, RH & Kirk, CJ (2004) Phytoestrogens are potent inhibitors of oestrogen sulfation: implications for breast cancer risk and treatment. Journal of Clinical Endocrinology and Metabolism 89, 17791787.CrossRefGoogle ScholarPubMed
Hilakivi-Clarke, L (2000) Oestrogens, BRCA1, and breast cancer. Cancer Research 60, 49935001.Google ScholarPubMed
Hilakivi-Clarke, L, Wang, C, Kalil, M, Riggins, R & Pestell, RG (2004) Nutritional modulation of the cell cycle and breast cancer. Endocrine-related Cancer 11, 603622.CrossRefGoogle ScholarPubMed
Horn, TL, Reichert, MA, Bliss, RL & Malejka-Giganti, D (2002) Modulations of P450 mRNA in liver and mammary gland and P450 activities and metabolism of oestrogen in liver by treatment of rats with indole-3-carbinol. Biochemical Pharmacology 64, 393404.CrossRefGoogle ScholarPubMed
Huang, CS, Shen, CY, Chang, KJ, Hsu, SM & Chern, HD (1999) Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. British Journal of Cancer 80, 18381843.CrossRefGoogle ScholarPubMed
Huber, JC, Schneeberger, C & Tempfer, CB (2002) Genetic modeling of oestrogen metabolism as a risk factor of hormone-dependent disorders. Maturitas 41, Suppl. 1, S55S64.CrossRefGoogle ScholarPubMed
International Agency for Research on Cancer (1983) Polynuclear Aromatic Compounds, Part 1. Chemical, Environmental and Experimental Data. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, vol. 32. Lyon, France: International Agency for Research on Cancer.Google Scholar
Ip, YT & Davis, RJ (1998) Signal transduction by the c-Jun N-terminal kinase (JNK) – from inflammation to development. Current Opinion in Cell Biology 10, 205219.CrossRefGoogle ScholarPubMed
Izumi, T, Piskula, MK, Osawa, S, Obata, A, Tobe, K, Saito, M, Kataoka, S, Kubota, Y & Kikuchi, M (2000) Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. Journal of Nutrition 130, 16951699.CrossRefGoogle ScholarPubMed
Jin, Z & MacDonald, RS (2002) Soy isoflavones increase latency of spontaneous mammary tumors in mice. Journal of Nutrition 132, 31863190.CrossRefGoogle ScholarPubMed
Jones, JL, Daley, BJ, Enderson, BL, Zhou, JR & Karlstad, MD (2002) Genistein inhibits tamoxifen effects on cell proliferation and cell cycle arrest in T47D breast cancer cells. American Surgeon 68, 575577.CrossRefGoogle ScholarPubMed
Ju, YH, Allred, CD, Allred, KF, Karko, KL, Doerge, DR & Helferich, WG (2001) Physiological concentrations of dietary genistein dose-dependently stimulate growth of oestrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. Journal of Nutrition 131, 29572962.CrossRefGoogle Scholar
Ju, YH, Doerge, DR, Allred, KF, Allred, CD & Helferich, WG (2002) Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Research 62, 24742477.Google ScholarPubMed
Katdare, M, Osborne, M & Telang, NT (2002) Soy isoflavone genistein modulates cell cycle progression and induces apoptosis in HER-2/neu oncogene expressing human breast epithelial cells. International Journal of Oncology 21, 809815.Google ScholarPubMed
Kleiner, HE, Vulimiri, SV, Reed, MJ, Uberecken, A & DiGiovanni, J (2002) Role of cytochrome P450 1a1 and 1b1 in the metabolic activation of 7,12-dimethylbenz[a]anthracene and the effects of naturally occurring furanocoumarins on skin tumor initiation. Chemical Research in Toxicology 15, 226235.CrossRefGoogle Scholar
Kronenberg, S, Esser, C & Carlberg, C (2000) An aryl hydrocarbon receptor conformation acts as the functional core of nuclear dioxin signaling. Nucleic Acids Research 28, 22862291.CrossRefGoogle ScholarPubMed
Kuiper, GG, Carlsson, B, Grandien, K, Enmark, E, Haggblad, J, Nilsson, S & Gustafsson, JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of oestrogen receptors alpha and beta. Endocrinology 138, 863870.CrossRefGoogle ScholarPubMed
Kuiper, GG, Lemmen, JG, Carlsson, B, Corton, JC, Safe, SH, van der Saag, PT, van der Burg, B & Gustafsson, JA (1998) Interaction of oestrogenic chemicals and phytoestrogens with oestrogen receptor beta. Endocrinology 139, 42524263.CrossRefGoogle Scholar
Kuo, SM (1997) Dietary flavonoid and cancer prevention: evidence and potential mechanism. Critical Reviews in Oncogenesis 8, 4769.CrossRefGoogle ScholarPubMed
Lamartiniere, CA, Cotroneo, MS, Fritz, WA, Wang, J, Mentor-Marcel, R & Elgavish, A (2002) Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. Journal of Nutrition 132, 552S558S.CrossRefGoogle ScholarPubMed
Le Bail, JC, Varnat, F, Nicolas, JC & Habrioux, G (1998) Oestrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids. Cancer Letters 130, 209216.CrossRefGoogle ScholarPubMed
Lee, H, Wang, HW, Su, HY & Hao, NJ (1994) The structure-activity relationships of flavonoids as inhibitors of cytochrome P-450 enzymes in rat liver microsomes and the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline. Mutagenesis 9, 101106.CrossRefGoogle ScholarPubMed
Lee, KM, Abel, J, Ko, Y, Harth, V, Park, WY, Seo, JS, Yoo, KY, Choi, JY, Shin, A, Ahn, SH, Noh, DY, Hirvonen, A & Kang, D (2003) Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women. British Journal of Cancer 88, 675678.CrossRefGoogle ScholarPubMed
Leung, LK, Do, L & Wang, TT (1998) Regulation of death promoter Bak expression by cell density and 17 beta-estradiol in MCF-7 cells. Cancer Letters 124, 4752.CrossRefGoogle ScholarPubMed
Leung, LK & Wang, TT (2000) Bcl-2 is not reduced in the death of MCF-7 cells at low genistein concentration. Journal of Nutrition 130, 29222926.CrossRefGoogle Scholar
Li, D, Wang, M, Dhingra, K & Hittelman, WN (1996) Aromatic DNA adducts in adjacent tissues of breast cancer patients: clues to breast cancer etiology. Cancer Research 56, 287293.Google ScholarPubMed
Li, F, Srinivasan, A, Wang, Y, Armstrong, RC, Tomaselli, KJ & Fritz, LC (1997) Cell-specific induction of apoptosis by microinjection of cytochrome c. Bcl-xL has activity independent of cytochrome c release. Journal of Biological Chemistry 272, 3029930305.CrossRefGoogle ScholarPubMed
Li, JJ & Li, SA (1987) Oestrogen carcinogenesis in Syrian hamster tissues: role of metabolism. Federation Proceedings 46, 18581863.Google ScholarPubMed
Li, Y, Bhuiyan, M & Sarkar, FH (1999 a) Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein. International Journal of Oncology 15, 525533.Google ScholarPubMed
Li, Y, Upadhyay, S, Bhuiyan, M & Sarkar, FH (1999 b) Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein. Oncogene 18, 31663172.CrossRefGoogle ScholarPubMed
Liao, CH, Pan, SL, Guh, JH & Teng, CM (2004) Genistein inversely affects tubulin-binding agent-induced apoptosis in human breast cancer cells. Biochemical Pharmology 67, 20312208.CrossRefGoogle ScholarPubMed
Liehr, JG (2000) Is estradiol a genotoxic mutagenic carcinogen? Endocrine Reviews 21, 4054.Google ScholarPubMed
Liehr, JG, Ulubelen, AA & Strobel, HW (1986) Cytochrome P-450-mediated redox cycling of oestrogens. Journal of Biological Chemistry 261, 1686516870.CrossRefGoogle Scholar
Liu, B, Edgerton, D, Yang, X, Kim, A, Ordonex-Ercan, D, Mason, T, Alvarez, K, McKimmey, C, Liu, N & Thor, A (2005) Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Cancer Research 65, 879886.CrossRefGoogle ScholarPubMed
Lowe, SW & Lin, AW (2000) Apoptosis in cancer. Carcinogenesis 21, 485495.CrossRefGoogle ScholarPubMed
MacDonald, CJ, Ciolino, HP & Yeh, GC (2001) Dibenzoylmethane modulates aryl hydrocarbon receptor function and expression of cytochromes P50 1A1, 1A2, and 1B1. Cancer Research 61, 39193924.Google ScholarPubMed
Makela, S, Poutanen, M, Lehtimaki, J, Kostian, ML, Santti, R & Vihko, R (1995) Oestrogen-specific 17 beta-hydroxysteroid oxidoreductase type 1 (EC. 1.1.1.62) as a possible target for the action of phytoestrogens. Proceedings of the Society for Experimental Biology and Medicine 208, 5159.CrossRefGoogle Scholar
Miodini, P, Fioravanti, L, Di Fronzo, G & Cappelletti, V (1999) The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. British Journal of Cancer 80, 11501155.CrossRefGoogle ScholarPubMed
Miyashita, T & Reed, JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80, 293299.Google ScholarPubMed
Montano, MM & Katzenellenbogen, BS (1997) The quinone reductase gene: a unique oestrogen receptor-regulated gene that is activated by antioestrogens. Proceedings of the National Academy of Sciences USA 94, 25812586.CrossRefGoogle Scholar
Morton, MS, Arisaka, O, Miyake, N, Morgan, LD & Evans, BA (2002) Phyto-oestrogen concentrations in serum from Japanese men and women over forty years of age. Journal of Nutrition 132, 31683171.CrossRefGoogle ScholarPubMed
Murata, M, Midorikawa, K, Koh, M, Umezawa, K & Kawanishi, S (2004) Genistein and daidzein induce cell proliferation and their metabolites cause oxidative DNA damage in relation to isoflavone-induced cancer of oestrogen-sensitive organs. Biochemistry 43, 25692577.CrossRefGoogle Scholar
Nenci, I, Marchetti, E & Querzoli, P (1988) Commentary on human mammary preneoplasia. The oestrogen receptor-promotion hypothesis. Journal of Steroid Biochemistry 30, 105106.CrossRefGoogle ScholarPubMed
Paech, K, Webb, P, Kuiper, GG, Nilsson, S, Gustafsson, J, Kushner, PJ & Scanlan, TS (1997) Differential ligand activation of oestrogen receptors ERalpha and ERbeta at AP1 sites. Science 277, 15081510.CrossRefGoogle ScholarPubMed
Perillo, B, Sasso, A, Abbondanza, C & Palumbo, G (2000) 17beta-Estradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two oestrogen-responsive elements present in the coding sequence. Molecular and Cellular Biology 20, 28902901.CrossRefGoogle Scholar
Peterson, G & Barnes, S (1991) Genistein inhibition of the growth of human breast cancer cells: independence from oestrogen receptors and the multi-drug resistance gene. Biochemical and Biophysical Research Communications 179, 661667.CrossRefGoogle ScholarPubMed
Pike, AC, Brzozowski, AM & Hubbard, RE (2000 a) A structural biologist's view of the oestrogen receptor. Journal of Steroid Biochemistry and Molecular Biology 74, 261268.CrossRefGoogle ScholarPubMed
Pike, AC, Brzozowski, AM, Walton, J, Hubbard, RE, Bonn, T, Gustafsson, JA & Carlquist, M (2000 b) Structural aspects of agonism and antagonism in the oestrogen receptor. Biochemical Society Transactions 28, 396400.CrossRefGoogle ScholarPubMed
Po, LS, Chen, ZY, Tsang, DS & Leung, LK (2002 a) Baicalein and genistein display differential actions on oestrogen receptor (ER) transactivation and apoptosis in MCF-7 cells. Cancer Letters 187, 3340.CrossRefGoogle ScholarPubMed
Po, LS, Wang, TT, Chen, ZY & Leung, LK (2002 b) Genistein-induced apoptosis in MCF-7 cells involves changes in Bak and Bcl-x without evidence of anti-oestrogenic effects. British Journal of Nutrition 88, 463469.CrossRefGoogle Scholar
Reed, JC (1994) Bcl-2 and the regulation of programmed cell death. Journal of Cell Biology 124, 16.CrossRefGoogle ScholarPubMed
Reed, JC (1998) Dysregulation of apoptosis in cancer. Cancer Journal from Scientific American 4, Suppl. 1, S8S14.Google ScholarPubMed
Reed, JC, Jurgensmeier, JM & Matsuyama, S (1998) Bcl-2 family proteins and mitochondria. Biochimica et Biophysica Acta 1366, 127137.CrossRefGoogle Scholar
Rowlands, JC, Berhow, MA & Badger, TM (2002) Oestrogenic and antiproliferative properties of soy sapogenols in human breast cancer cells in vitro. Food and Chemical Toxicology 40, 17671774.CrossRefGoogle ScholarPubMed
Safe, S (2001) Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicology Letters 120, 17.CrossRefGoogle Scholar
Satoh, H, Nishikawa, K, Suzuki, K, Asano, R, Virgona, N, Ichikawa, T, Hagiwara, K & Yano, T (2003) Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent. Research Communications in Molecular Pathology and Pharmacology 113114, 149158.Google Scholar
Sergeev, IN (2004) Genistein induces Ca2+-mediated, calpain/caspase-12-dependent apoptosis in breast cancer cells. Biochemical and Biophysical Research Communications 321, 462467.CrossRefGoogle ScholarPubMed
Shao, ZM, Wu, J, Shen, ZZ & Barsky, SH (1998) Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Research 58, 48514857.Google ScholarPubMed
Sheng, ZM, Marchetti, A, Buttitta, F, Champeme, MH, Campani, D, Bistocchi, M, Lidereau, R & Callahan, R (1996) Multiple regions of chromosome 6q affected by loss of heterozygosity in primary human breast carcinomas. British Journal of Cancer 73, 144147.CrossRefGoogle ScholarPubMed
Shimizu, Y, Nakatsuru, Y, Ichinose, M, Takahashi, Y, Kume, H, Mimura, J, Fujii-Kuriyama, Y & Ishikawa, T (2000) Benzo‘a’pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proceedings of the National Academy of Sciences USA 97, 779782.CrossRefGoogle ScholarPubMed
So, FV, Guthrie, N, Chambers, AF & Carroll, KK (1997) Inhibition of proliferation of oestrogen receptor-positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess oestrogen. Cancer Letters 112, 127133.CrossRefGoogle Scholar
Taioli, E, Bradlow, HL, Garbers, SV, Sepkovic, DW, Osborne, MP, Trachman, J, Ganguly, S & Garte, SJ (1999) Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detection and Prevention 23, 232237.CrossRefGoogle ScholarPubMed
Upadhyay, S, Neburi, M, Chinni, SR, Alhasan, S, Miller, F & Sarkar, FH (2001) Differential sensitivity of normal and malignant breast epithelial cells to genistein is partly mediated by p21(WAF1). Clinical Cancer Research 7, 17821789.Google ScholarPubMed
Valachovicova, T, Slivova, V, Bergman, H, Shuherk, J & Sliva, D (2004) Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathyways. International Journal of Oncology 25, 13891395.Google Scholar
Vissac-Sabatier, C, Bignon, YJ, Bernard-Gallon, DJ (2003) Effects of the phytoestrogens genistein and daidzein on BRCA2 tumor suppressor gene expression in breast cell lines. Nutrition and Cancer 45, 247255.CrossRefGoogle ScholarPubMed
Wang, C & Kurzer, MS (1997) Phyto-oestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutrition and Cancer 28, 236247.CrossRefGoogle ScholarPubMed
Wang, TT & Phang, JM (1995) Effects of oestrogen on apoptotic pathways in human breast cancer cell line MCF-7. Cancer Research 55, 24872489.Google ScholarPubMed
Wang, TT, Sathyamoorthy, N & Phang, JM (1996) Molecular effects of genistein on oestrogen receptor mediated pathways. Carcinogenesis 17, 271275.CrossRefGoogle ScholarPubMed
Yager, JD (2000) Endogenous oestrogens as carcinogens through metabolic activation. Journal of the National Cancer Institute. Monographs 6773CrossRefGoogle ScholarPubMed
Yang, NN, Bryant, HU, Hardikar, S, Sato, M, Galvin, RJ, Glasebrook, AL & Termine, JD (1996) Oestrogen and raloxifene stimulate transforming growth factor-beta 3 gene expression in rat bone: a potential mechanism for oestrogen- or raloxifene-mediated bone maintenance. Endocrinology 137, 20752084.CrossRefGoogle ScholarPubMed
Yang, NN, Venugopalan, M, Hardikar, S & Glasebrook, A (1996) Identification of an oestrogen response element activated by metabolites of 17beta-estradiol and raloxifene. Science 273, 12221225.CrossRefGoogle ScholarPubMed
Yared, E, McMillan, TJ & Martin, FL (2002) Genotoxic effects of oestrogens in breast cells detected by the micronucleus assay and the Comet assay. Mutagenesis 17, 345352.CrossRefGoogle ScholarPubMed
Yoshidome, K, Shibata, MA, Couldrey, C, Korach, KS & Green, JE (2000) Oestrogen promotes mammary tumor development in C3(1)/SV40 large T-antigen transgenic mice: paradoxical loss of oestrogen receptoralpha expression during tumor progression. Cancer Research 60, 69016910.Google ScholarPubMed
Zhang, F, Swanson, SM, van Breemen, RB, Liu, X, Yang, Y, Gu, C & Bolton, JL (2001) Equine oestrogen metabolite 4-hydroxyequilenin induces DNA damage in the rat mammary tissues: formation of single-strand breaks, apurinic sites, stable adducts, and oxidized bases. Chemical Research in Toxicology 14, 16541659.CrossRefGoogle ScholarPubMed
Zhang, Y, Hendrich, S & Murphy, PA (2003) Glucuronides are the main isoflavone metabolites in women. Journal of Nutrition 133, 399404.CrossRefGoogle ScholarPubMed
Zheng, W, Xie, DW, Jin, F, Cheng, JR, Dai, Q, Wen, WQ, Shu, XO & Gao, YT (2000) Genetic polymorphism of cytochrome P450-1B1 and risk of breast cancer. Cancer Epidemiology, Biomarkers and Prevention 9, 147150.Google ScholarPubMed
Zhu, BT & Conney, AH (1998) Functional role of oestrogen metabolism in target cells: review and perspectives. Carcinogenesis 19, 127.CrossRefGoogle ScholarPubMed
Ziegler, RG, Hoover, RN, Pike, MC, Hildesheim, A, Nomura, AM, West, DW, Wu-Williams, AH, Kolonel, LN, Horn-Ross, PL, Rosenthal, JF & Hyer, MB (1993) Migration patterns and breast cancer risk in Asian-American women. Journal of the National Cancer Institute 85, 18191827.CrossRefGoogle ScholarPubMed