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. 1994 Oct 1;303(Pt 1):199–205. doi: 10.1042/bj3030199

Regulation of the expression of alkaline phosphatase in a human breast-cancer cell line.

T C Chang 1, J K Wang 1, M W Hung 1, C H Chiao 1, L C Tsai 1, G G Chang 1
PMCID: PMC1137576  PMID: 7945240

Abstract

Treatment of the cultured human breast-cancer cells BC-M1 with dexamethasone induced a placental-type alkaline phosphatase (ALP). Both the ALP activity and the mRNA level in the cells were increased. The induction of ALP activity by dexamethasone was time- and dose-dependent. The accumulation of ALP mRNA was inhibited by both actinomycin D and cycloheximide, indicating that its induction is a complex event and may involve other regulatory proteins. Retinoic acid showed opposing effects with dexamethasone on the expression of alkaline phosphatase. Retinoic acid (RA) and phorbol 12-myristate 13-acetate also substantially reduced the dexamethasone-induced expression of ALP. Studies on thermostability and sensitivity to various amino acid inhibitors indicated that the BC-M1 ALP is most similar to the placental form. Northern hybridization analysis also revealed that ALP mRNA transcripts in BC-M1 and term placenta are similar in size and are distinct from that of the placental-like mRNA transcript in choriocarcinoma cells. Analysis of the degradation of BC-M1 ALP mRNA showed a similar half-life of 27 h in the untreated and in dexamethasone- or RA-treated cells. These findings demonstrated that the induction of ALP in BC-M1 cells by dexamethasone is mainly due to the increase in the transcription of the ALP gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albert J. L., Sundstrom S. A., Lyttle C. R. Estrogen regulation of placental alkaline phosphatase gene expression in a human endometrial adenocarcinoma cell line. Cancer Res. 1990 Jun 1;50(11):3306–3310. [PubMed] [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  4. Chang T. C., Huang S. M., Huang T. M., Chang G. G. Human placental alkaline phosphatase. An improved purification procedure and kinetic studies. Eur J Biochem. 1992 Oct 1;209(1):241–247. doi: 10.1111/j.1432-1033.1992.tb17282.x. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Chou J. Y., Takahashi S. Control of placental alkaline phosphatase gene expression in HeLa cells: induction of synthesis by prednisolone and sodium butyrate. Biochemistry. 1987 Jun 16;26(12):3596–3602. doi: 10.1021/bi00386a052. [DOI] [PubMed] [Google Scholar]
  7. Di Lorenzo D., Albertini A., Zava D. Progestin regulation of alkaline phosphatase in the human breast cancer cell line T47D. Cancer Res. 1991 Aug 15;51(16):4470–4475. [PubMed] [Google Scholar]
  8. Diamond D. J., Goodman H. M. Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine. Transcriptional rate and mRNA stability changes in pituitary tumor cells. J Mol Biol. 1985 Jan 5;181(1):41–62. doi: 10.1016/0022-2836(85)90323-7. [DOI] [PubMed] [Google Scholar]
  9. Diamond M. I., Miner J. N., Yoshinaga S. K., Yamamoto K. R. Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science. 1990 Sep 14;249(4974):1266–1272. doi: 10.1126/science.2119054. [DOI] [PubMed] [Google Scholar]
  10. Fishman W. H. Oncotrophoblast gene expression: placental alkaline phosphatase. Adv Cancer Res. 1987;48:1–35. doi: 10.1016/s0065-230x(08)60689-2. [DOI] [PubMed] [Google Scholar]
  11. Fraker L. D., Halter S. A., Forbes J. T. Growth inhibition by retinol of a human breast carcinoma cell line in vitro and in athymic mice. Cancer Res. 1984 Dec;44(12 Pt 1):5757–5763. [PubMed] [Google Scholar]
  12. Ghosh N. K., Rukenstein A., Baltimore R., Cox R. P. Studies on hormonal induction of alkaline phosphatase in HeLa cell cultures. Kinetic, thermodynamic and electrophoretic properties of induced and base-level enzymes. Biochim Biophys Acta. 1972 Nov 24;286(1):175–185. doi: 10.1016/0304-4165(72)90103-1. [DOI] [PubMed] [Google Scholar]
  13. Green E., Todd B., Heath D. Mechanism of glucocorticoid regulation of alkaline phosphatase gene expression in osteoblast-like cells. Eur J Biochem. 1990 Feb 22;188(1):147–153. doi: 10.1111/j.1432-1033.1990.tb15382.x. [DOI] [PubMed] [Google Scholar]
  14. Hanford W. C., Kottel R. H., Fishman W. H. Alkaline phosphatase protein increases in response to prednisolone in HeLa cells. Biochem J. 1981 Nov 15;200(2):461–464. doi: 10.1042/bj2000461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Harris H. Multilocus enzyme systems and the evolution of gene expression: the alkaline phosphatases as a model example. Harvey Lect. 1980;76:95–124. [PubMed] [Google Scholar]
  16. Harris H. The human alkaline phosphatases: what we know and what we don't know. Clin Chim Acta. 1990 Jan 15;186(2):133–150. doi: 10.1016/0009-8981(90)90031-m. [DOI] [PubMed] [Google Scholar]
  17. Imai Y., Rodan S. B., Rodan G. A. Effects of retinoic acid on alkaline phosphatase messenger ribonucleic acid, catecholamine receptors, and G proteins in ROS 17/2.8 cells. Endocrinology. 1988 Feb;122(2):456–463. doi: 10.1210/endo-122-2-456. [DOI] [PubMed] [Google Scholar]
  18. Lange P. H., Millan J. L., Stigbrand T., Vessella R. L., Ruoslahti E., Fishman W. H. Placental alkaline phosphatase as a tumor marker for seminoma. Cancer Res. 1982 Aug;42(8):3244–3247. [PubMed] [Google Scholar]
  19. Majeska R. J., Nair B. C., Rodan G. A. Glucocorticoid regulation of alkaline phosphatase in the osteoblastic osteosarcoma cell line ROS 17/2.8. Endocrinology. 1985 Jan;116(1):170–179. doi: 10.1210/endo-116-1-170. [DOI] [PubMed] [Google Scholar]
  20. Marth C., Böck G., Daxenbichler G. Effect of 4-hydroxyphenylretinamide and retinoic acid on proliferation and cell cycle of cultured human breast cancer cells. J Natl Cancer Inst. 1985 Nov;75(5):871–875. doi: 10.1093/jnci/75.5.871. [DOI] [PubMed] [Google Scholar]
  21. Millán J. L. Molecular cloning and sequence analysis of human placental alkaline phosphatase. J Biol Chem. 1986 Mar 5;261(7):3112–3115. [PubMed] [Google Scholar]
  22. Mulkins M. A., Allison A. C. Recombinant human interleukin-1 inhibits the induction by dexamethasone of alkaline phosphatase activity in murine capillary endothelial cells. J Cell Physiol. 1987 Dec;133(3):539–545. doi: 10.1002/jcp.1041330315. [DOI] [PubMed] [Google Scholar]
  23. Nakayama T., Yoshida M., Kitamura M. L-leucine sensitive, heat-stable alkaline-phosphatase isoenzyme detected in a patient with pleuritis carcinomatosa. Clin Chim Acta. 1970 Nov;30(2):546–548. doi: 10.1016/0009-8981(70)90152-x. [DOI] [PubMed] [Google Scholar]
  24. Ng K. W., Manji S. S., Young M. F., Findlay D. M. Opposing influences of glucocorticoid and retinoic acid on transcriptional control in preosteoblasts. Mol Endocrinol. 1989 Dec;3(12):2079–2085. doi: 10.1210/mend-3-12-2079. [DOI] [PubMed] [Google Scholar]
  25. Ovitt C. E., Strauss A. W., Alpers D. H., Chou J. Y., Boime I. Expression of different-sized placental alkaline phosphatase mRNAs in placenta and choriocarcinoma cells. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3781–3785. doi: 10.1073/pnas.83.11.3781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pan C. J., Sartwell A. D., Chou J. Y. Transcriptional regulation and the effects of sodium butyrate and glycosylation on catalytic activity of human germ cell alkaline phosphatase. Cancer Res. 1991 Apr 15;51(8):2058–2062. [PubMed] [Google Scholar]
  27. Perrella F. W. EZ-FIT: a practical curve-fitting microcomputer program for the analysis of enzyme kinetic data on IBM-PC compatible computers. Anal Biochem. 1988 Nov 1;174(2):437–447. doi: 10.1016/0003-2697(88)90042-5. [DOI] [PubMed] [Google Scholar]
  28. Sakiyama T., Robinson J. C., Chou J. Y. Multiple forms of alkaline phosphatase in untreated and 5-bromo-2'-deoxyuridine-treated choriocarcinoma cells. Arch Biochem Biophys. 1978 Dec;191(2):782–791. doi: 10.1016/0003-9861(78)90420-4. [DOI] [PubMed] [Google Scholar]
  29. Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
  30. Sehgal P. B., Darnell J. E., Jr, Tamm I. The inhibition by DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) of hnRNA and mRNA production in HeLa cells. Cell. 1976 Nov;9(3):473–480. doi: 10.1016/0092-8674(76)90092-1. [DOI] [PubMed] [Google Scholar]
  31. Stigbrand T., Millán J. L., Fishman W. H. The genetic basis of alkaline phosphatase isozyme expression. Isozymes Curr Top Biol Med Res. 1982;6:93–117. [PubMed] [Google Scholar]
  32. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wahren B., Holmgren P. A., Stigbrand T. Placental alkaline phosphatase, alphafetoprotein and carcinoembryonic antigen in testicular tumors. Tissue typing by means of cytologic smears. Int J Cancer. 1979 Dec 15;24(6):749–753. doi: 10.1002/ijc.2910240608. [DOI] [PubMed] [Google Scholar]
  34. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  35. Zava D. T., McGuire W. L. Estrogen receptor. Unoccupied sites in nuclei of a breast tumor cell line. J Biol Chem. 1977 Jun 10;252(11):3703–3708. [PubMed] [Google Scholar]

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