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British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Sep;68(3):530–536. doi: 10.1038/bjc.1993.381

Retinoic acid receptors in retinoid responsive ovarian cancer cell lines detected by polymerase chain reaction following reverse transcription.

H Harant 1, I Korschineck 1, G Krupitza 1, B Fazeny 1, C Dittrich 1, T W Grunt 1
PMCID: PMC1968390  PMID: 8353043

Abstract

The growth inhibitory effects of all-trans and 13-cis retinoic acid (RA) and of the synthetic retinoids TTNPB, TTNPB-ethylester and TTNN were studied on seven human epithelial ovarian cancer cell lines and one ovarian teratocarcinoma cell line. Six of seven ovarian adenocarcinoma cell lines were inhibited in their growth by RA and by synthetic retinoids in a dose dependent manner. No response to these substances was observed for the ovarian teratocarcinoma cell line. The knowledge that RA and retinoids exert their action on the cells via nuclear receptors led us to examine the expression of RAR-alpha, -beta and -gamma mRNA by these cell lines by polymerase chain reaction following reverse transcription. All cell lines expressed RAR-alpha and -gamma mRNA and six of the eight cell lines were found to express additionally RAR-beta mRNA, among them the ovarian teratocarcinoma cell line. Our data indicate that there was no direct association between the presence of RAR subtype transcripts and the response to retinoids in ovarian cancer cell lines.

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Selected References

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  1. Aström A., Pettersson U., Krust A., Chambon P., Voorhees J. J. Retinoic acid and synthetic analogs differentially activate retinoic acid receptor dependent transcription. Biochem Biophys Res Commun. 1990 Nov 30;173(1):339–345. doi: 10.1016/s0006-291x(05)81062-9. [DOI] [PubMed] [Google Scholar]
  2. Benbrook D., Lernhardt E., Pfahl M. A new retinoic acid receptor identified from a hepatocellular carcinoma. Nature. 1988 Jun 16;333(6174):669–672. doi: 10.1038/333669a0. [DOI] [PubMed] [Google Scholar]
  3. Brand N., Petkovich M., Krust A., Chambon P., de Thé H., Marchio A., Tiollais P., Dejean A. Identification of a second human retinoic acid receptor. Nature. 1988 Apr 28;332(6167):850–853. doi: 10.1038/332850a0. [DOI] [PubMed] [Google Scholar]
  4. Broxterman H. J., Sprenkels-Schotte C., Engelen P., Leyva A., Pinedo H. M. Analysis of human ascites effect on clonogenic growth of human tumor cell lines and NRK-49F cells in soft agar. Int J Cell Cloning. 1987 Mar;5(2):158–169. doi: 10.1002/stem.5530050208. [DOI] [PubMed] [Google Scholar]
  5. Buick R. N., Pullano R., Trent J. M. Comparative properties of five human ovarian adenocarcinoma cell lines. Cancer Res. 1985 Aug;45(8):3668–3676. [PubMed] [Google Scholar]
  6. 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]
  7. De Luca L. M. Retinoids and their receptors in differentiation, embryogenesis, and neoplasia. FASEB J. 1991 Nov;5(14):2924–2933. [PubMed] [Google Scholar]
  8. Delescluse C., Cavey M. T., Martin B., Bernard B. A., Reichert U., Maignan J., Darmon M., Shroot B. Selective high affinity retinoic acid receptor alpha or beta-gamma ligands. Mol Pharmacol. 1991 Oct;40(4):556–562. [PubMed] [Google Scholar]
  9. Eichele G. Retinoids and vertebrate limb pattern formation. Trends Genet. 1989 Aug;5(8):246–251. doi: 10.1016/0168-9525(89)90096-6. [DOI] [PubMed] [Google Scholar]
  10. Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
  11. Glass C. K., Lipkin S. M., Devary O. V., Rosenfeld M. G. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell. 1989 Nov 17;59(4):697–708. doi: 10.1016/0092-8674(89)90016-0. [DOI] [PubMed] [Google Scholar]
  12. Graupner G., Malle G., Maignan J., Lang G., Pruniéras M., Pfahl M. 6'-substituted naphthalene-2-carboxylic acid analogs, a new class of retinoic acid receptor subtype-specific ligands. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1554–1561. doi: 10.1016/0006-291x(91)91750-7. [DOI] [PubMed] [Google Scholar]
  13. Grunt T. W., Somay C., Ellinger A., Pavelka M., Dittrich E., Dittrich C. The differential effects of N,N-dimethylformamide and transforming growth factor-beta 1 on a human ovarian cancer cell line (HOC-7). J Cell Physiol. 1992 Apr;151(1):13–22. doi: 10.1002/jcp.1041510104. [DOI] [PubMed] [Google Scholar]
  14. Grunt T. W., Somay C., Oeller H., Dittrich E., Dittrich C. Comparative analysis of the effects of dimethyl sulfoxide and retinoic acid on the antigenic pattern of human ovarian adenocarcinoma cells. J Cell Sci. 1992 Oct;103(Pt 2):501–509. doi: 10.1242/jcs.103.2.501. [DOI] [PubMed] [Google Scholar]
  15. Hamilton T. C., Young R. C., McKoy W. M., Grotzinger K. R., Green J. A., Chu E. W., Whang-Peng J., Rogan A. M., Green W. R., Ozols R. F. Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983 Nov;43(11):5379–5389. [PubMed] [Google Scholar]
  16. Heyman R. A., Mangelsdorf D. J., Dyck J. A., Stein R. B., Eichele G., Evans R. M., Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992 Jan 24;68(2):397–406. doi: 10.1016/0092-8674(92)90479-v. [DOI] [PubMed] [Google Scholar]
  17. Hill B. T., Whelan R. D., Gibby E. M., Sheer D., Hosking L. K., Shellard S. A., Rupniak H. T. Establishment and characterisation of three new human ovarian carcinoma cell lines and initial evaluation of their potential in experimental chemotherapy studies. Int J Cancer. 1987 Feb 15;39(2):219–225. doi: 10.1002/ijc.2910390216. [DOI] [PubMed] [Google Scholar]
  18. Hong W. K., Lippman S. M., Itri L. M., Karp D. D., Lee J. S., Byers R. M., Schantz S. P., Kramer A. M., Lotan R., Peters L. J. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med. 1990 Sep 20;323(12):795–801. doi: 10.1056/NEJM199009203231205. [DOI] [PubMed] [Google Scholar]
  19. Hu L., Crowe D. L., Rheinwald J. G., Chambon P., Gudas L. J. Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res. 1991 Aug 1;51(15):3972–3981. [PubMed] [Google Scholar]
  20. Huang M. E., Ye Y. C., Chen S. R., Chai J. R., Lu J. X., Zhoa L., Gu L. J., Wang Z. Y. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567–572. [PubMed] [Google Scholar]
  21. Krust A., Kastner P., Petkovich M., Zelent A., Chambon P. A third human retinoic acid receptor, hRAR-gamma. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5310–5314. doi: 10.1073/pnas.86.14.5310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lippman S. M., Meyskens F. L., Jr Results of the use of vitamin A and retinoids in cutaneous malignancies. Pharmacol Ther. 1989;40(1):107–122. doi: 10.1016/0163-7258(89)90078-8. [DOI] [PubMed] [Google Scholar]
  23. Lippman S. M., Parkinson D. R., Itri L. M., Weber R. S., Schantz S. P., Ota D. M., Schusterman M. A., Krakoff I. H., Gutterman J. U., Hong W. K. 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst. 1992 Feb 19;84(4):235–241. doi: 10.1093/jnci/84.4.235. [DOI] [PubMed] [Google Scholar]
  24. Mangelsdorf D. J., Ong E. S., Dyck J. A., Evans R. M. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature. 1990 May 17;345(6272):224–229. doi: 10.1038/345224a0. [DOI] [PubMed] [Google Scholar]
  25. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  26. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  27. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  28. Pratt M. A., Kralova J., McBurney M. W. A dominant negative mutation of the alpha retinoic acid receptor gene in a retinoic acid-nonresponsive embryonal carcinoma cell. Mol Cell Biol. 1990 Dec;10(12):6445–6453. doi: 10.1128/mcb.10.12.6445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  30. Somay C., Grunt T. W., Mannhalter C., Dittrich C. Relationship of myc protein expression to the phenotype and to the growth potential of HOC-7 ovarian cancer cells. Br J Cancer. 1992 Jul;66(1):93–98. doi: 10.1038/bjc.1992.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Umesono K., Giguere V., Glass C. K., Rosenfeld M. G., Evans R. M. Retinoic acid and thyroid hormone induce gene expression through a common responsive element. Nature. 1988 Nov 17;336(6196):262–265. doi: 10.1038/336262a0. [DOI] [PubMed] [Google Scholar]
  32. Yu V. C., Delsert C., Andersen B., Holloway J. M., Devary O. V., När A. M., Kim S. Y., Boutin J. M., Glass C. K., Rosenfeld M. G. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell. 1991 Dec 20;67(6):1251–1266. doi: 10.1016/0092-8674(91)90301-e. [DOI] [PubMed] [Google Scholar]
  33. de Thé H., Vivanco-Ruiz M. M., Tiollais P., Stunnenberg H., Dejean A. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature. 1990 Jan 11;343(6254):177–180. doi: 10.1038/343177a0. [DOI] [PubMed] [Google Scholar]

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