Abstract
The expressions of cyclins A, D1 and E at the protein level were investigated by Western blotting in human colorectal carcinomas and in adjacent non-neoplastic colorectal mucosas. Cyclin E was higher in the cancer tissue than in the non-neoplastic mucosa in 92% patients (35 out of 38 cases). However, the cyclin A expression of the mucosa was higher than that of the cancer tissue in 63% (25 out of 40 cases) cases, and only 4 (10%) cancers had higher cyclin A expression. Eleven cancers (27%) demonstrated expression equivalent to that in the mucosa. Equal expression of cyclin D1 in cancer and mucosal tissues was found in 51% cases (20/39), lower expression of cyclin D1 by cancer tissues was demonstrated in 41% cases (16/39) and only three cancers showed higher expression than the mucosa. Proliferating-cell nuclear antigen immunohistochemistry revealed that the labeling index of the cancer tissue was 43.5±8.3% while that of the mucosa was only 14.8±5.1%. These results proved that colorectal cancers express high levels of cyclin E, consistent with a high rate of cell proliferation, whereas most of such cancer lose control of cyclin A and cyclin D1 expression.
Similar content being viewed by others
Abbreviations
- PCNA :
-
proliferating-cell nuclear antigen
- Cdk :
-
cyclin-dependent kinase
- Cdc :
-
cell division cycle
References
Biasco G, Paganelli GM, Miglioli M, Barbara L (1992) Cell proliferation biomarkers in the gastrointestinal tract. J Cell Biochem (Suppl) 16G:73–78
Bartkova J, Jiri L, Heiko M, Dorrit L, Micheal S, Bartek J (1994a) Cyclin D1 protein expression and function in human breast cancer. Int J Cancer 57:353–361
Bartkova J, Lukas J, Strauss M, Bartek J (1994b) The PRAD-1/ cyclin D1 oncogene product accumulates aberrantly in a subset of colorectal carcinomas. Int J Cancer 58:568–573
Dou Q, Levin AH, Zhao S, Pardee AB (1993) Cyclin E and cyclin A as candidates for the restriction point protein. Cancer Res 53:1493–1497
Hall PA, Levision DA, Woods AL, C.C-W. Y, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R, Waseem NH, Lane DP (1990) Proliferation cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162:285–294
Jansen-Durr P, Meichle A, Steiner P, Pagano M, Finke K, Nitz J Wessbecher J, Draette G, Eilers M (1993) Differential modulation of cyclin gene expression by MYC. Proc Natl Acad Sci USA 90:3685–3689
Jiang W, Kahn SM, Tomita N, Zhang YJ, Lu SH, Weinstein IB (1992) Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res 52:2980–2983
Keyomarsi K, Pardee AB (1993) Redundant cyclin overexpression and gene amplification in breast cancer cells. Proc Natl Acad Sci USA 90:1112–1116
Knoblich JA, Sauer K, Jones L, Richardson H, Saint R, Lehner CF (1994) Cyclin E controls S phase progression and its downregulation duringDrosophila embryogenesis is required for the arrest of cell proliferation. Cell 77:107–120
Koff A, Cross F, Fisher A, Schumacher J, Legullec K, Philippe M, Roberts JM (1991) Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell 66:1217–1228
Kosaka C, Sasaguki T, Masuda J, Zen K, Shimokado K, Yokota T, Ogata J (1993) Protein kinase C-mediated inhibition of cyclin A expression in human vascular endothelial cells. Biochem Biophys Res Commun 193:991–998
Leach FS, Elledge SJ, Cherr CJ, Willson JKV, Markowitz S, Kinzler KW, Vogelstein B (1993) Amplification of cyclin genes in colorectal carcinomas. Cancer Res 53:1986–1989
Lew DJ, Dulic V, Reed SI (1991) Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell 66:1197–1206
Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A (1991) A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 350:512–515
Ohtsubo M, Roberts JM (1993) Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science 259:1908–1912
Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G (1992) Cyclin A is required at two points in the human cell cycle. EMBO J 11:961–971
Paterlini P, Suberville AM, Zindy F, Melle J, Sonnier M, Marie JP, Dreyfus F, Brechot C (1993) Cyclin A expression in human hematological malignancies: a new marker of cell proliferation. Cancer Res 53:235–238
Pines J, Hunter T (1990) Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B. Nature 346:760–763
Quelle DE, Ashun RA, Shurtleff SA, Kato JY, Bar-sagi D, Rousse IMF, Sherr CJ (1993) Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev 7:1559–1571
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Sherr CJ (1993) Mammalian G1 cyclins. Cell 73:1059–1065
Terpstra OT, Van Blankenstein M, Dees J, Eilers GM (1987) Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. Gastroenterology 97:704–708
Wang A, Yoshimi N, Tanaka T, Mori H (1994) The inhibitory effect of magnesium hydroxide on the bile acid-induced cell proliferation of colon epithelium in rats with comparison to the action of calcium lactate. Carcinogenesis 15:2661–2663
Wang J, Chenivess X, Henglein B, Brechot C (1990) Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 343:555–557
Xiong Y, Connolly T, Futcher B, Beach D (1991) Human D-type cyclin. Cell 65:691–699
Zhang YJ, Jiang W, Chen CJ, Lee CS, Kahn SM, Santella RM, Weinstein IB (1993) Amplification and overexprssion of cyclin D1 in human hepatocellular carcinoma. Biochem Biophys Res Commun 196:1010–1016
Zindy F, Lamas E, Chenivesse X, Sobczak J, Wang J, Fesquet D, Henglein B, Brechot C (1992) Cyclin A is required in normal epithelial cells. Biochem Biophys Res Commun 182:1144–1154
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wang, A., Yoshimi, N., Suzui, M. et al. Different expression patterns of cyclins A, D1 and E in human colorectal cancer. J Cancer Res Clin Oncol 122, 122–126 (1996). https://doi.org/10.1007/BF01226270
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01226270