Abstract
Microarray technology was used to gain an insight into the molecular events of tumor cell growth inhibition mediated by the soy isoflavone genistein. For this, a susceptible bladder tumor line TCCSUP was treated with the inhibitory dose (50 µM) of genistein for various periods of time, followed by mRNA isolations, cDNA probe preparations, and hybridization individually to cDNA chips containing 884 sequence-verified known human genes. After analyzing the hybridization signals with a simple quantitative method developed by this study, we detected thategr-1, whose expression has been associated with proliferation and differentiation, was transiently induced and this expression pattern was later confirmed by RT-PCR. Thus, microarray technology is a reliable and powerful tool for profiling gene expression patterns in many biological systems related to cancer. We further detected many groups of genes with distinct expression profiles and most of them encode for proteins that regulate the signal transduction or the cell cycle pathways. These genes warrant further investigation as regards their roles in the susceptibility of the tumor cell line to the antitumor drug.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adlercreutz CH, Goldin BR, Gorbach SL, Hockerstedt KA, Watanabe S, Hamalainen EK, Markkanen MH, Makela TH, Whala KT, Hase TA, Fotsis T. Soybean phytoestrogen intake and cancer risk. J Nutr 125:757s-770s;1995.
Aguda BD. A quantitative analysis of the kinetics of the G(2) DNA damage checkpoint system. Proc Natl Acad Sci USA 96:11352–11357;1999.
Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S-I, Itoh N, Shibuya M, Fukami Y. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262:5592–5595;1987.
Chen C-J, Chuang Y-C, Lin T-M, Wu H-Y. Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: High-arsenic artesian well water and cancers. Cancer Res 45:5895–5899;1985.
Chen JJW, Wu R, Yang P-C, Huang J-Y, Sher Y-P, Han M H, Kao W-C, Lee P-J, Chiu TF, Chang F, Chu Y-W, Wu C-W, Peck K. Profiling expression patterns and isolating differentially expressed genes by cDNA microarray system with colorimetry detection. Genomics 51:313–324;1998.
Chiang HH, Hwang I, Goodman HM. Isolation of the Arabidopsis GA4 locus. Plant Cell 7:195–201;1995.
Cohen DR, Curran T. The structure and function of the fos proto-oncogene. Crit Rev Oncog 1:65–88;1989.
Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863–14868;1998.
Fotsis T, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R, Schweigerer L. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA 90:2690–2694;1993.
Innocente SA, Abrahamson JL, Cogswell JP, Lee JM. p53 regulates a G2 checkpoint through cyclin B1. Proc Natl Acad Sci USA 96:2147–2152;1999.
Lennon G, Auffray C, Polymeropoulos M, Soares MB. The I.M.A.G.E. Consortium: An integrated molecular analysis of genomes and their expression. Genomics 33:151–152;1996.
Leustek T, Murillo M, Cervantes M. Cloning of a cDNA encoding ATP sulfurylase fromArabidopsis thaliana by functional expression inSaccharomyces cerevisiae. Plant Physiol 105:897–902;1994.
Li C, Mitchell DH, Coleman DL. Analysis of Egr-1 protein induction in murine peritoneal macrophages treated with granulocyte-macrophage colony-stimulating factor. Yale J Biol Med 67:269–276;1994.
Liu J, Lacy J, Sukhatme VP, Coleman DL. Granulocyte-macrophage colony-stimulating factor induces transcriptional activation of Egr-1 in murine peritoneal macrophages. J Biol Chem 266:5929–5933;1991.
Logan HM, Cathala N, Grignon C, Davidian JC. Cloning of a cDNA encoded by a member of theArabidopsis thaliana ATP sulfurylase multigene family. Expression studies in yeast and in relation to plant sulfur nutrition. J Biol Chem 271:12227–12233;1996.
Markovits J, Linassier C, Fosse P, Couprie J, Pierre J, Jacquemin-Sablon A, Saucier J-M, Le Pecq J-B, Larsen AK. Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res 49:5111–5117;1989.
Mathews MB, Bernstein RM, Franza BR Jr, Garrels JI. Identity of the proliferating cell nuclear antigen and cyclin. Nature 309:374–376;1984.
Millward TA, Hess D, Hemmings BA. Ndr protein kinase is regulated by phosphorylation on two conserved sequence motifs. J Biol Chem 274:33847–33850;1999.
Murphy M, Stinnakre MG, Senamaud-Beaufort C, Winston NJ, Sweenery C, Kubelka M, Carrington M, Brechot C, Sobczak-Thepot J. Delayed early embryonic lethality following disruption of the murine cyclin A2 gene. Nat Genet 15:83–86;1997.
Naim M, Gestetner B, Bondi A, Birk Y. Antioxidative and antihemolytic activities of soybean isoflavone. J Agric Food Chem 24:1174–1177;1976.
Nayak SK, O'Toole C, Price ZH. A cell line from an anaplastic transitional cell carcinoma of human urinary bladder. Br J Cancer 35:142–151;1977.
Nguyen HQ, Hoffman-Liebermann B, Liebermann DA. The zinc finger transcription factor Egr-1 is essential for and restricts differentiation along the macrophage lineage. Cell 72:197–209;1993.
Ogawara H, Akiyama T, Ishida J, Watanabe S-I, Suzuki K. A specific inhibitor for tyrosine protein kinase from Pseudomonas. J Antibiot 39:606–608;1986.
Pan B-J, Hong Y-J, Chang G-C, Wang M-T, Cinkotai FF, Ko Y-C. Excess cancer mortality among children and adolescents in residential districts polluted by petrochemical manufacturing plants in Taiwan. J Toxicol Environ Health 43:117–129;1994.
Pasero P, Duncker BP, Schwob E, Gasser SM. A role for the Cdc7 kinase regulatory subunit Dbf4p in the formation of initiation-competent origins of replication. Genes Dev 13:2159–2176;1999.
Schena M, Davis RW. Structure of homeoboxleucine zipper genes suggests a model for the evolution of gene families. Proc Natl Acad Sci USA 91:8393–8397;1994.
Su I-J, Chen W-J, Lin T-M. High prevalence of transitional cell carcinoma in endemic area of chronic arsenicism in Taiwan. Chin J Oncol Soc 1:29–36;1985.
Wang H-J, Murphy PA. Isoflavone composition of American and Japanese soybean in Iowa: Effects of variety, crop year, and location. J Agric Food Chem 42:1674–1677;1994.
Yeh MY, Yu DS, Chen SC, Lin MS, Chang SY, Ma CP, Han SH. Establishment and characterization of a human urinary bladder carcinoma cell line (TSGH-8301). J Surg Oncol 37:177–184;1988.
Zhang H, Kobayashi R, Galaktionov K, Beach D. p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phage kinase. Cell 22:915–925;1995.
Zhou J-R, Mukherjee P, Gugger ET, Tanaka T, Blackburn GL, Clinton SK. Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis. Cancer Res 58:5231–5238;1998.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chen, CC., Shieh, B., Jin, YT. et al. Microarray profiling of gene expression patterns in bladder tumor cells treated with genistein. J Biomed Sci 8, 214–222 (2001). https://doi.org/10.1007/BF02256415
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02256415