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Genistein-induced proteome changes in the human endometrial carcinoma cell line, ishikawa

Clinical Proteomics volume 2, pages 153–167 (2006)Cite this article

Abstract

Epidemiological studies have shown that Asian populations display a lower incidence of hormone-dependant cancers, cardiovascular disease, osteoporosis, and menopausal ailments compared to Western societies. Available data support the proposal that lower incidence is associated with the high dietary consumption of isoflavones, such as genistein. This study used two-dimensional electrophoresis to characterize the effect of genistein on the proteome of an endometrial tumor cell model, namely the Ishikawa cell line. Proteome maps displaying approx 1800 proteins were obtained from cells treated with vehicle or genistein at physiologically attainable concentrations of 0.5, 5, or 50 μM or supra-physiological concentration, 500 μM. The effects of genistein on protein expression were characterized using image analysis software. A total 65 protein spots displayed a significant decrease in expression and 32 proteins displayed a significant increase in expression. Of these protein spots, 29 were randomly selected for characterization by matrix assisted laser desorption/ionization tandem mass spectrometry, yielding 18 different proteins. This type of analysis enabled the characterization of a wide range of cellular proteins and allowed for the identification of functional and biochemical pathways that may be regulated or affected by genistein, including cellular transcription, cell proliferation, stress response, or modulation of oncogenic pathways.

References

  1. Knight, D. C. and Eden, J. A. (1995) Phytoestrogens: a short review.Maturitas 22, 167–175.

    Article  PubMed  CAS  Google Scholar 

  2. Bingham, S. A., Atkinson, C., Liggins, J., Bluck, L., and Coward, A. (1998) Phytooestrogens: where are we now?Br. J. Nutr. 79, 393–406.

    Article  PubMed  CAS  Google Scholar 

  3. Dijsselbloem, N., Vanden Berghe, W., De Naeyer, A., and Haegeman, G. (2004) Soy isoflavone phyto-pharmaceuticals in interleukin-6 affections. Multi-purpose nutraceuticals at the crossroad of hormone replacement, anti-cancer and anti-inflammatory therapy.Biochem. Pharmacol. 68, 1171–1185.

    Article  PubMed  CAS  Google Scholar 

  4. Nagata, C., Takatsuka, N., Kurisu, Y., and Shimizu, H. (1998) Decreased serum total cholesterol concentration is associated with high intake of soy products in Japanese men and women.J. Nutr. 128, 209–213.

    PubMed  CAS  Google Scholar 

  5. Liao, C. H., Pan, S. L., Guh, J. H., and Teng, C. M. (2004) Genistein inversely affects tubulin-binding agent-induced apoptosis in human breast cancer cells.Biochem. Pharmacol. 67, 2031–2038.

    Article  PubMed  CAS  Google Scholar 

  6. Magee, P. J., McGlynn, H., and Rowland, I. R. (2004) Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro.Cancer Lett. 208, 35–41.

    Article  PubMed  CAS  Google Scholar 

  7. Markovits, J., Linassier, C., Fosse, P., et al. (1989) Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II.Cancer Res. 49, 5111–5117.

    PubMed  CAS  Google Scholar 

  8. Li, Y. and Sarkar, F. H. (2002) Inhibition of nuclear factor kappaB activation in PC3 cells by genistein is mediated via Akt signaling pathway.Clin. Cancer Res. 8, 2369–2377.

    PubMed  CAS  Google Scholar 

  9. Akiyama, T., Ishida, J., Nakagawa, S., et al. (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases.J. Biol. Chem. 262, 5592–5595.

    PubMed  CAS  Google Scholar 

  10. Casagrande, F. and Darbon, J. M. (2001) Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1.Biochem. Pharmacol. 61, 1205–1215.

    Article  PubMed  CAS  Google Scholar 

  11. Chinni, S. R., Alhasan, S. A., Multani, A. S., Pathak, S., and Sarkar, F. H. (2003) Pleotropic effects of genistein on MCF-7 breast cancer cells.Int. J. Mol. Med. 12, 29–34.

    PubMed  CAS  Google Scholar 

  12. Salti, G. I., Grewal, S., Mehta, R. R., Das Gupta, T. K., Boddie, A. W., Jr., Constantinou, A. I. (2000) Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells.Eur. J. Cancer 36, 796–802.

    Article  PubMed  CAS  Google Scholar 

  13. Fuchs, D., Erhard, P., Rimbach, G., Daniel, H., and Wenzel, U. (2005) Genistein blocks homocystein-induced alterations in the proteome of human endothelial cells.Proteomics 5, 2808–1288.

    Article  PubMed  CAS  Google Scholar 

  14. Adachi, T., Okuno, Y., Takenaka, S., et al. (2005) Comprehensive analysis of the effect of phytoestrogen, daidzein, on a testicular cell line, using mRNA and protein expression profile.Food Chem. Toxicol. 43, 529–535.

    Article  PubMed  CAS  Google Scholar 

  15. Fuchs, D., Erhard, P., Turner, R., Rimbach, G., Daniel, H., and Wenzel, U. (2005) Genistein reverses changes of the proteome induced by oxidized-LDL in EA.hy 926 human endothelial cells.J. Proteome Res. 4, 369–376.

    Article  PubMed  CAS  Google Scholar 

  16. Fuchs, D., de Pascual-Teresa, S., Rimbach, G., et al. (2005) Proteome analysis for identification of target proteins of genistein in primary human endothelial cells stressed with oxidized LDL or homocysteine.Eur. J. Nutr. 44, 95–104.

    Article  PubMed  CAS  Google Scholar 

  17. Rowell, C., Carpenter, D. M., and Lamartiniere, C. A. (2005) Chemoprevention of breast cancer, proteomic discovery of genistein action in the rat mammary gland.J. Nutr. 135, 2953S-2959S.

    PubMed  CAS  Google Scholar 

  18. Xu, X., Harris, K. S., Wang, H. J., Murphy, P. A., and Hendrich, S. (1995) Bioavailability of soybean isoflavones depends upon gut microflora in women.J. Nutr. 125, 2307–2315.

    PubMed  CAS  Google Scholar 

  19. Bloedon, L. T., Jeffcoat, A. R., Lopaczynski, W., et al. (2002) Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women.Am. J. Clin. Nutr. 76, 1126–1137.

    PubMed  CAS  Google Scholar 

  20. Busby, M. G., Jeffcoat, A. R., Bloedon, L. T. et al. (2002) Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men.Am. J. Clin. Nutr. 75, 126–136.

    PubMed  CAS  Google Scholar 

  21. Coldham, N. G. and Sauer, M. J. (2000) Pharmacokinetics of [(14)C]Genistein in the rat: gender-related differences, potential mechanisms of biological action, and implications for human health.Toxicol. Appl. Pharmacol. 164, 206–215.

    Article  PubMed  CAS  Google Scholar 

  22. Farhan, H., Wahala, K., Adlercreutz, H., and Cross, H. S. (2002) Isoflavonoids inhibit catabolism of vitamin D in prostate cancer cells.J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 777, 261–268.

    Article  PubMed  CAS  Google Scholar 

  23. Cordwell, S. J., Basseal, D. J., Bjellqvist, B., Shaw, D. C., and Humphery-Smith, I. (1997) Characterisation of basic proteins from Spiroplasma melliferum using novel immobilised pH gradients.Electrophoresis 18, 1393–1398.

    Article  PubMed  CAS  Google Scholar 

  24. Immler, D., Gremm, D., Kirsch, D., Spengler, B., Presek, P., Meyer, H. E. (1998) Identification of phosphorylated proteins from thrombin-activated human platelets isolated by two-dimensional gel electrophoresis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS).Electrophoresis 19, 1015–1023.

    Article  PubMed  CAS  Google Scholar 

  25. Dunn, M. J. (1987) Two-dimensional gel electrophoresis of proteins.J. Chromatogr. 418, 145–185.

    Article  PubMed  CAS  Google Scholar 

  26. Ohta, H., Sakamoto, H., and Satoh, K. (1998) In vitro effects of gonadotropin-releasing hormone (GnRH) analogue on cancer cell sensitivity to cis-platinum.Cancer Lett. 134, 111–118.

    Article  PubMed  CAS  Google Scholar 

  27. Gorg, A., Obermaier, C., Boguth, G., et al. (2000) The current state of two-dimensional electrophoresis with immobilized pH gradients.Electrophoresis 21, 1037–1053.

    Article  PubMed  CAS  Google Scholar 

  28. Nawrocki, A., Larsen, M. R., Podtelejnikov, A. V., et al. (1998) Correlation of acidic and basic carrier ampholyte and immobilized pH gradient two-dimensional gel electrophoresis patterns based on mass spectrometric protein identification.Electrophoresis 19, 1024–1035.

    Article  PubMed  CAS  Google Scholar 

  29. Gobom, J., Nordhoff, E., Mirgorodskaya, E., Ekman, R., and Roepstorff, P. (1999) Sample purification and preparation technique based on nano-scale reversed-phase columns for the sensitive analysis of complex peptide mixtures by matrix-assisted laser desorption/ionization mass spectrometry.J. Mass. Spectrom. 34, 105–116.

    Article  PubMed  CAS  Google Scholar 

  30. Larsen, M. R., Cordwell, S. J., and Roepstorff, P. (2002) Graphite powder as an alternative or supplement to reversed-phase material for desalting and concentration of peptide mixtures prior to matrix-assisted laser desorption/ionization-mass spectrometry.Proteomics 2, 1277–1287.

    Article  PubMed  CAS  Google Scholar 

  31. Perkins, D. N., Pappin, D. J., Creasy, D. M., and Cottrell, J. S. (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data.Electrophoresis 20, 3551–3567.

    Article  PubMed  CAS  Google Scholar 

  32. Larsen, M. R. and Roepstorff, P. (2000) Mass spectrometric identification of proteins and characterization of their post-translational modifications in proteome analysis.Fresenius J. Anal. Chem. 366, 677–690.

    Article  PubMed  CAS  Google Scholar 

  33. Kawauchi, K., Lazarus, A. H., Sanghera, J. S., Man, G. L., Pelech, S. L., and Delovitch, T. L. (1996) Regulation of BCR-and PKC/Ca(2+)-mediated activation of the Raf1/MEK/MAPK pathway by protein-tyrosine kinase and-tyrosine phosphatase activities.Mol. Immunol. 33, 287–296.

    Article  PubMed  CAS  Google Scholar 

  34. Davis, J. N., Kucuk, O., and Sarkar, F. H. (1999) Genistein inhibits NF-kappa B activation in prostate cancer cells.Nutr. Cancer 35, 167–174.

    Article  PubMed  CAS  Google Scholar 

  35. Schmidt, E. V. (2004) The role of c-myc in regulation of translation initiation.Oncogene 23, 3217–3221.

    Article  PubMed  CAS  Google Scholar 

  36. Schmidt, E. V. (1999) The role of c-myc in cellular growth control.Oncogene 18, 2988–2996.

    Article  PubMed  CAS  Google Scholar 

  37. Rosenwald, I. B. (2004) The role of translation in neoplastic transformation from a pathologist’s point of view.Oncogene 23, 3230–3247.

    Article  PubMed  CAS  Google Scholar 

  38. Secombe, J., Pierce, S. B., and Eisenman, R. N. (2004) Myc: a weapon of mass destruction.Cell 117, 153–156.

    Article  PubMed  CAS  Google Scholar 

  39. Niederacher, D., An, H. X., Cho, Y. J., Hantschmann, P., Bender, H. G., and Beckmann, M. W. (1999) Mutations and amplification of oncogenes in endometrial cancer.Oncology 56, 59–65.

    Article  PubMed  CAS  Google Scholar 

  40. Borst, M. P., Baker, V. V., Dixon, D., Hatch, K. D., Shingleton, H. M., and Miller, D. M. (1990) Oncogene alterations in endometrial carcinoma.Gynecol. Oncol. 38, 364–366.

    Article  PubMed  CAS  Google Scholar 

  41. Bai, M. K., Costopoulos, J. S., Christoforidou, B. P., and Papadimitriou, C. S. (1994) Immunohistochemical detection of the c-myc oncogene product in normal, hyperplastic and carcinomatous endometrium.Oncology 51, 314–319.

    Article  PubMed  CAS  Google Scholar 

  42. Geisler, J. P., Geisler, H. E., Manahan, K. J. et al. (2004) Nuclear and cytoplasmic c-myc staining in endometrial carcinoma and their relationship to survival.Int. J. Gynecol. Cancer 14, 133–137.

    Article  PubMed  CAS  Google Scholar 

  43. Kim, J. H., Paek, K. Y., Choi, K., et al. (2003) Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner.Mol. Cell. Biol. 23, 708–720.

    Article  PubMed  CAS  Google Scholar 

  44. Byrjalsen, I., Mose Larsen, P., Fey, S. J., Nilas, L., Larsen, M. R., and Christiansen, C. (1999) Two-dimensional gel analysis of human endometrial proteins: characterization of proteins with increased expression in hyperplasia and adenocarcinoma.Mol. Hum. Reprod. 5, 748–756.

    Article  PubMed  CAS  Google Scholar 

  45. Shah, Y. M., Basrur, V., and Rowan, B. G. (2004) Selective estrogen receptor modulator regulated proteins in endometrial cancer cells.Mol. Cell. Endocrinol. 219, 127–139.

    Article  PubMed  CAS  Google Scholar 

  46. Evans, J. R., Mitchell, S. A., Spriggs, K. A., et al. (2003) Members of the poly (rC) binding protein family stimulate the activity of the c-myc internal ribosome entry segment in vitro and in vivo.Oncogene 22, 8012–8020.

    Article  PubMed  CAS  Google Scholar 

  47. Yan, C. H., Chen, X. G., Li, Y., and Han, R. (1999) Effects of genistein, a soybean-derived isoflavone, on proliferation and differentiation of B16-BL6 mouse melanoma cells.J. Asian Nat. Prod. Res. 1, 285–299.

    Article  PubMed  CAS  Google Scholar 

  48. Yang, Y., Yoo, H. M., Choi, I., Pyun, K. H., Byun, S. M., and Ha, H. (1996) Interleukin 4-induced proliferation in normal human keratinocytes is associated with c-myc gene expression and inhibited by genistein.J. Invest. Dermatol. 107, 367–372.

    Article  PubMed  CAS  Google Scholar 

  49. Ouchi, H., Ishiguro, H., Ikeda, N., Hori, M., Kubota, Y., and Uemura, H. (2005) Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity.Int. J. Urol. 12, 73–80.

    Article  PubMed  CAS  Google Scholar 

  50. Konstantakopoulos, N., Montgomery, K. G., Chamberlain, N., et al. (2006) Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells.Mol. Carcinog. 45, 752–763.

    Article  PubMed  CAS  Google Scholar 

  51. Etienne-Manneville, S. and Hall, A. (2002) Rho GTPases in cell biology.Nature 420, 629–635.

    Article  PubMed  CAS  Google Scholar 

  52. Crespo, P. and Leon, J. (2000) Ras proteins in the control of the cell cycle and cell differentiation.Cell. Mol. Life Sci. 57, 1613–1636.

    Article  PubMed  CAS  Google Scholar 

  53. Yeh, E., Cunningham, M., Arnold, H., et al. (2004) A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells.Nat. Cell Biol. 6, 308–318.

    Article  PubMed  CAS  Google Scholar 

  54. Shinohara, N. and Koyanagi, T. (2002) Ras signal transduction in carcinogenesis and progression of bladder cancer: molecular target for treatment?Urol. Res. 30, 273–281.

    Article  PubMed  CAS  Google Scholar 

  55. Lucas, L., Penalva, V., Ramirez de Molina, A., Del Peso, L., and Lacal, J. C. (2002) Modulation of phospholipase D by Ras proteins mediated by its effectors Ral-GDS, PI3K and Raf-1.Int. J. Oncol. 21, 477–485.

    PubMed  CAS  Google Scholar 

  56. Drew, J. E., Bown, D., and Gatehouse, J. A. (1993) Sequence of a novel plant ras-related cDNA from Pisum sativum.Plant Mol. Biol. 21, 1195–1199.

    Article  PubMed  CAS  Google Scholar 

  57. Lilja, J. F., Wu, D., Reynolds, R. K., and Lin, J. (2001) Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.Anticancer Res. 21, 1969–1974.

    PubMed  CAS  Google Scholar 

  58. Myung, J. K., Afjehi-Sadat, L., Felizardo-Cabatic, M., Slavc, I., and Lubec, G. (2004) Expressional patterns of chaperones in ten human tumor cell lines.Proteome Sci. 2, 8.

    Article  PubMed  CAS  Google Scholar 

  59. Dastoor, Z. and Dreyer, J. (2000) Nuclear translocation and aggregate formation of heat shock cognate protein 70 (Hsc70) in oxidative stress and apoptosis.J. Cell Sci. 113, 2845–2854.

    PubMed  CAS  Google Scholar 

  60. Turner, C. P., Panter, S. S., and Sharp, F. R. (1999) Anti-oxidants prevent focal rat brain injury as assessed by induction of heat shock proteins (HSP70, HO-1/HSP32, HSP47) following subarachnoid injections of lysed blood.Brain Res. Mol. Brain Res. 65, 87–102.

    Article  PubMed  CAS  Google Scholar 

  61. Maeda, A., Ohguro, H., Maeda, T., et al. (2000) Aberrant expression of photoreceptor-specific calcium-binding protein (recoverin) in cancer cell lines.Cancer Res. 60, 1914–1920.

    PubMed  CAS  Google Scholar 

  62. Yehiely, F. and Oren, M. (1992) The gene for the rat heat-shock cognate, hsc70, can suppress oncogene-mediated transformation.Cell. Growth Differ. 3, 803–809.

    PubMed  CAS  Google Scholar 

  63. O’Neill, P. A., Shaaban, A. M., West, C. R., et al. (2004) Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27.Br. J. Cancer 90, 182–188.

    Article  PubMed  CAS  Google Scholar 

  64. Leonardi, R., Villari, L., Caltabiano, M., and Travali, S. (2001) Heat shock protein 27 expression in the epithelium of periapical lesions.J. Endod. 27, 89–92.

    Article  PubMed  CAS  Google Scholar 

  65. Sheth, K., De, A., Nolan, B., et al. (2001) Heat shock protein 27 inhibits apoptosis in human neutrophils.J. Surg. Res. 99, 129–133.

    Article  PubMed  CAS  Google Scholar 

  66. Faucher, C., Capdevielle, J., Canal, I., et al. (1993) The 28-kDa protein whose phosphorylation is induced by protein kinase C activators in MCF-7 cells belongs to the family of low molecular mass heat shock proteins and is the estrogen-regulated 24-kDa protein.J. Biol. Chem. 268, 15,168–15,173.

    CAS  Google Scholar 

  67. Korneeva, I., Bongiovanni, A. M., Girotra, M., Caputo, T. A., and Witkin, S. S. (2000) IgA antibodies to the 27-kDa heat-shock protein in the genital tracts of women with gynecologic cancers.Int. J. Cancer 87, 824–828.

    Article  PubMed  CAS  Google Scholar 

  68. Korneeva, I., Bongiovanni, A. M., Girotra, M., Caputo, T. A., and Witkin, S. S. (2000) Serum antibodies to the 27-kd heat shock protein in women with gynecologic cancers.Am. J. Obstet. Gynecol. 183, 18–21.

    PubMed  CAS  Google Scholar 

  69. Shnyder, S. D. and Hubbard, M. J. (2002) ERp29 is a ubiquitous resident of the endoplasmic reticulum with a distinct role in secretory protein production.J. Histochem. Cytochem. 50, 557–566.

    PubMed  CAS  Google Scholar 

  70. Ferrari, D. M., Nguyen Van, P., Kratzin, H. D., and Soling, H. D. (1998) ERp28, a human endoplasmic-reticulum-lumenal protein, is a member of the protein disulfide isomerase family but lacks a CXXC thioredoxin-box motif.Eur. J. Biochem. 255, 570–579.

    Article  PubMed  CAS  Google Scholar 

  71. Dissemond, J., Busch, M., Kothen, T., et al. (2004) Differential downregulation of endo-plasmic reticulum-residing chaperones calnexin and calreticulin in human metastatic melanoma.Cancer Lett. 203, 225–231.

    Article  PubMed  CAS  Google Scholar 

  72. Molinari, M., Eriksson, K. K., Calanca, V., et al. (2004) Contrasting functions of calreticulin and calnexin in glycoprotein folding and ER quality control.Mol. Cell. 13, 125–135.

    Article  PubMed  CAS  Google Scholar 

  73. Pike, S. E., Yao, L., Setsuda, J., et al. (1999) Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth.Blood 94, 2461–2468.

    PubMed  CAS  Google Scholar 

  74. Yao, L., Pike, S. E., and Tosato, G. (2002) Laminin binding to the calreticulin fragment vasostatin regulates endothelial cell function.J. Leukoc. Biol. 71, 47–53.

    PubMed  CAS  Google Scholar 

  75. Pike, S. E., Yao, L., Jones, K. D., et al. (1998) Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth.J. Exp. Med. 188, 2349–2356.

    Article  PubMed  CAS  Google Scholar 

  76. McCallum, C. D., Do, H., Johnson, A. E., and Frydman, J. (2000) The interaction of the chaperonin tailless complex polypeptide 1 (TCP1) ring complex (TRiC) with ribosome-bound nascent chains examined using photo-cross-linking.J. Cell. Biol. 149, 591–602.

    Article  PubMed  CAS  Google Scholar 

  77. Yokota, S., Yanagi, H., Yura, T., and Kubota, H. (2001) Cytosolic chaperonin-containing t-complex polypeptide 1 changes the content of a particular subunit species concomitant with substrate binding and folding activities during the cell cycle.Eur. J. Biochem. 268, 4664–4673.

    Article  PubMed  CAS  Google Scholar 

  78. Yokota, S., Yanagi, H., Yura, T., and Kubota, H. (1999) Cytosolic chaperonin is up-regulated during cell growth. Preferential expression and binding to tubulin at G(1)/S transition through early S phase.J. Biol. Chem. 274, 37,070–37,078.

    CAS  Google Scholar 

  79. Yokota, S., Yamamoto, Y., Shimizu, K., et al. (2001) Increased expression of cytosolic chaperonin CCT in human hepatocellular and colonic carcinoma.Cell Stress Chaperones 6, 345–350.

    Article  PubMed  CAS  Google Scholar 

  80. Weinmann, A. S., Bartley, S. M., Zhang, T., Zhang, M. Q., and Farnham, P. J. (2001) Use of chromatin immunoprecipitation to clone novel E2F target promoters.Mol. Cell. Biol. 21, 6820–6832.

    Article  PubMed  CAS  Google Scholar 

  81. Walsh, M. J., Shue, G., Spidoni, K., and Kapoor, A. (1995) E2F-1 and a cyclin-like DNA repair enzyme, uracil-DNA glycosylase, provide evidence for an autoregulatory mechanism for transcription.J. Biol. Chem. 270, 5289–5298.

    Article  PubMed  CAS  Google Scholar 

  82. Fusaro, G., Dasgupta, P., Rastogi, S., Joshi, B., and Chellappan, S. (2003) Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling.J. Biol. Chem. 278, 47,853–47,861.

    Article  CAS  Google Scholar 

  83. Fusaro, G., Wang, S., and Chellappan, S. (2002) Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis.Oncogene 21, 4539–4548.

    Article  PubMed  CAS  Google Scholar 

  84. Altenberg, B. and Greulich, K. O. (2004) Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes.Genomics 84, 1014–1020.

    Article  PubMed  CAS  Google Scholar 

  85. Sathe, S. S., Sizemore, N., Li, X., et al. (2004) Mutant human cells with constitutive activation of NF-kappaB.Proc. Natl. Acad. Sci. USA 101, 192–197.

    Article  PubMed  CAS  Google Scholar 

  86. Hu, M. C., Wang, Y., Qiu, W. R., Mikhail, A., Meyer, C. F., and Tan, T. H. (1999) Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase.Oncogene 18, 5514–5524.

    Article  PubMed  CAS  Google Scholar 

  87. Dhawan, P. and Richmond, A. (2002) A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells.J. Biol. Chem. 277, 7920–7928.

    Article  PubMed  CAS  Google Scholar 

  88. Dhawan, P. and Richmond, A. (2002) Role of CXCL1 in tumorigenesis of melanoma.J. Leukoc. Biol. 72, 9–18.

    PubMed  CAS  Google Scholar 

  89. Choi, C., Cho, H., Park, J., Cho, C., and Song, Y. (2003) Suppressive effects of genistein on oxidative stress and NFkappaB activation in RAW 264.7 macrophages.Biosci. Biotechnol. Biochem. 67, 1916–1922.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Gynaecological Cancer Research Centre, Royal Women’s Hospital, 3053, Carlton, Victoria, Australia

    Nicki Konstantakopoulos, Michael A. Quinn & Gregory E. Rice

  2. Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia

    Nicki Konstantakopoulos, Michael A. Quinn & Harry M. Georgiou

  3. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark

    Martin R. Larsen

  4. VBCRC Cancer Genetics Laboratory, Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria, Australia

    Ian G. Campbell

  5. Australian Proteome Analysis Facility, Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia

    Mark S. Baker

  6. Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia

    Harry M. Georgiou

  7. Translational Proteomics, Baker Medcal Research Institute, Melbourne, Australia

    Gregory E. Rice

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  1. Nicki Konstantakopoulos
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Konstantakopoulos, N., Larsen, M.R., Campbell, I.G. et al. Genistein-induced proteome changes in the human endometrial carcinoma cell line, ishikawa. Clin Proteom 2, 153–167 (2006). https://doi.org/10.1007/BF02752498

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Clinical Proteomics

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