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. 1992 Oct;141(4):973–980.

Localization of cellular retinoid-binding proteins in human cervical intraepithelial neoplasia and invasive carcinoma.

P Hillemanns 1, L Tannous-Khuri 1, J P Koulos 1, D Talmage 1, T C Wright Jr 1
PMCID: PMC1886642  PMID: 1329518

Abstract

Cellular retinoic acid-binding protein (CRABP) and cellular retinol-binding protein (CRBP) were localized in biopsies of normal squamous epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell cancer of the cervix uteri by immunohistochemistry. In both the normal stratified squamous epithelium of the exocervix and low-grade CIN, CRABP I was present predominantly in the basal layer of the epithelium. The more superficial, differentiated cell layers lacked immunoreactive protein. In high-grade CIN (CIN2-3), the distribution of CRABP I was altered. Immunoreactive CRABP I was detected in all layers of high-grade CIN. In squamous cell carcinoma of the cervix, CRABP I was detected in cells throughout the tumor but was minimal in cells demonstrating squamous differentiation. In contrast to CRABP I, CRBP was diffusely present throughout the cervical epithelium irrespective of the state of differentiation or the presence of disease.

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Selected References

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

  1. 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]
  2. Blaner W. S., Goodman D. S. Purification and properties of plasma retinol-binding protein. Methods Enzymol. 1990;189:193–206. doi: 10.1016/0076-6879(90)89290-x. [DOI] [PubMed] [Google Scholar]
  3. Burge S. M. Darier's disease and other dyskeratoses: response to retinoids. Pharmacol Ther. 1989;40(1):75–90. doi: 10.1016/0163-7258(89)90076-4. [DOI] [PubMed] [Google Scholar]
  4. Chu E. W., Malmgren R. A. An inhibitory effect of vitamin A on the induction of tumors of forestomach and cervix in the Syrian hamster by carcinogenic polycyclic hydrocarbons. Cancer Res. 1965 Jul;25(6):884–895. [PubMed] [Google Scholar]
  5. Chytil F., Ong D. E. Intracellular vitamin A--binding proteins. Annu Rev Nutr. 1987;7:321–335. doi: 10.1146/annurev.nu.07.070187.001541. [DOI] [PubMed] [Google Scholar]
  6. Dencker L., Annerwall E., Busch C., Eriksson U. Localization of specific retinoid-binding sites and expression of cellular retinoic-acid-binding protein (CRABP) in the early mouse embryo. Development. 1990 Oct;110(2):343–352. doi: 10.1242/dev.110.2.343. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Goodman D. S. Vitamin A and retinoids in health and disease. N Engl J Med. 1984 Apr 19;310(16):1023–1031. doi: 10.1056/NEJM198404193101605. [DOI] [PubMed] [Google Scholar]
  9. Gorodeski G. I., Eckert R. L., Utian W. H., Sheean L., Rorke E. A. Cultured human ectocervical epithelial cell differentiation is regulated by the combined direct actions of sex steroids, glucocorticoids, and retinoids. J Clin Endocrinol Metab. 1990 Jun;70(6):1624–1630. doi: 10.1210/jcem-70-6-1624. [DOI] [PubMed] [Google Scholar]
  10. Gorodeski G. I., Eckert R. L., Utian W. H., Sheean L., Rorke E. A. Retinoids, sex steroids and glucocorticoids regulate ectocervical cell envelope formation but not the level of the envelope precursor, involucrin. Differentiation. 1989 Dec;42(2):75–80. doi: 10.1111/j.1432-0436.1989.tb00609.x. [DOI] [PubMed] [Google Scholar]
  11. Graham S. Epidemiology of retinoids and cancer. J Natl Cancer Inst. 1984 Dec;73(6):1423–1428. [PubMed] [Google Scholar]
  12. Hill D. L., Grubbs C. J. Retinoids as chemopreventive and anticancer agents intact animals (review). Anticancer Res. 1982 Jan-Apr;2(1-2):111–124. [PubMed] [Google Scholar]
  13. Jetten A. M. Multi-stage program of differentiation in human epidermal keratinocytes: regulation by retinoids. J Invest Dermatol. 1990 Nov;95(5 Suppl):44S–46S. doi: 10.1111/1523-1747.ep12505757. [DOI] [PubMed] [Google Scholar]
  14. Kanai M., Raz A., Goodman D. S. Retinol-binding protein: the transport protein for vitamin A in human plasma. J Clin Invest. 1968 Sep;47(9):2025–2044. doi: 10.1172/JCI105889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kanerva L. O., Johansson E., Niemi K. M., Lauharanta J., Salo O. P. Epidermodysplasia verruciformis. Clinical and light- and electron-microscopic observations during etretinate therapy. Arch Dermatol Res. 1985;278(2):153–160. doi: 10.1007/BF00409223. [DOI] [PubMed] [Google Scholar]
  16. Kato M., Blaner W. S., Mertz J. R., Das K., Kato K., Goodman D. S. Influence of retinoid nutritional status on cellular retinol- and cellular retinoic acid-binding protein concentrations in various rat tissues. J Biol Chem. 1985 Apr 25;260(8):4832–4838. [PubMed] [Google Scholar]
  17. Kato M., Kato K., Blaner W. S., Chertow B. S., Goodman D. S. Plasma and cellular retinoid-binding proteins and transthyretin (prealbumin) are all localized in the islets of Langerhans in the rat. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2488–2492. doi: 10.1073/pnas.82.8.2488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kato M., Kato K., Goodman D. S. Immunocytochemical studies on the localization of plasma and of cellular retinol-binding proteins and of transthyretin (prealbumin) in rat liver and kidney. J Cell Biol. 1984 May;98(5):1696–1704. doi: 10.1083/jcb.98.5.1696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. La Vecchia C., Franceschi S., Decarli A., Gentile A., Fasoli M., Pampallona S., Tognoni G. Dietary vitamin A and the risk of invasive cervical cancer. Int J Cancer. 1984 Sep 15;34(3):319–322. doi: 10.1002/ijc.2910340306. [DOI] [PubMed] [Google Scholar]
  20. Lippman S. M., Kessler J. F., Meyskens F. L., Jr Retinoids as preventive and therapeutic anticancer agents (Part I). Cancer Treat Rep. 1987 Apr;71(4):391–405. [PubMed] [Google Scholar]
  21. 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]
  22. Lotan R. Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta. 1980 Mar 12;605(1):33–91. doi: 10.1016/0304-419x(80)90021-9. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Manoharan K., Rao A. R. Inhibitory actions of retinoic acid and butylated hydroxyanisole on cervical carcinogenesis induced by 3-methylcholanthrene in mouse. Indian J Exp Biol. 1984 Apr;22(4):195–198. [PubMed] [Google Scholar]
  25. Marshall J. R., Graham S., Byers T., Swanson M., Brasure J. Diet and smoking in the epidemiology of cancer of the cervix. J Natl Cancer Inst. 1983 May;70(5):847–851. [PubMed] [Google Scholar]
  26. Meyskens F. L., Jr, Graham V., Chvapil M., Dorr R. T., Alberts D. S., Surwit E. A. A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia. J Natl Cancer Inst. 1983 Nov;71(5):921–925. [PubMed] [Google Scholar]
  27. Noy N., Blaner W. S. Interactions of retinol with binding proteins: studies with rat cellular retinol-binding protein and with rat retinol-binding protein. Biochemistry. 1991 Jul 2;30(26):6380–6386. doi: 10.1021/bi00240a005. [DOI] [PubMed] [Google Scholar]
  28. Ottonello S., Petrucco S., Maraini G. Vitamin A uptake from retinol-binding protein in a cell-free system from pigment epithelial cells of bovine retina. Retinol transfer from plasma retinol-binding protein to cytoplasmic retinol-binding protein with retinyl-ester formation as the intermediate step. J Biol Chem. 1987 Mar 25;262(9):3975–3981. [PubMed] [Google Scholar]
  29. Palan P. R., Romney S. L. Cellular binding proteins for vitamin A in human carcinomas and in normal tissues. Cancer Res. 1980 Nov;40(11):4221–4224. [PubMed] [Google Scholar]
  30. 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]
  31. Romney S. L., Dwyer A., Slagle S., Duttagupta C., Palan P. R., Basu J., Calderin S., Kadish A. Chemoprevention of cervix cancer: Phase I-II: A feasibility study involving the topical vaginal administration of retinyl acetate gel. Gynecol Oncol. 1985 Jan;20(1):109–119. doi: 10.1016/0090-8258(85)90131-3. [DOI] [PubMed] [Google Scholar]
  32. Romney S. L., Palan P. R., Duttagupta C., Wassertheil-Smoller S., Wylie J., Miller G., Slagle N. S., Lucido D. Retinoids and the prevention of cervical dysplasias. Am J Obstet Gynecol. 1981 Dec 15;141(8):890–894. doi: 10.1016/s0002-9378(16)32680-1. [DOI] [PubMed] [Google Scholar]
  33. Schindler J., Matthaei K. I., Sherman M. I. Isolation and characterization of mouse mutant embryonal carcinoma cells which fail to differentiate in response to retinoic acid. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1077–1080. doi: 10.1073/pnas.78.2.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sherman M. I., Matthaei K. I., Schindler J. Studies on the mechanism of induction of embryonal carcinoma cell differentiation by retinoic acid. Ann N Y Acad Sci. 1981 Feb 27;359:192–199. doi: 10.1111/j.1749-6632.1981.tb12747.x. [DOI] [PubMed] [Google Scholar]
  35. Siegenthaler G., Saurat J. H., Ponec M. Terminal differentiation in cultured human keratinocytes is associated with increased levels of cellular retinoic acid-binding protein. Exp Cell Res. 1988 Sep;178(1):114–126. doi: 10.1016/0014-4827(88)90383-7. [DOI] [PubMed] [Google Scholar]
  36. Tabin C. J. Retinoids, homeoboxes, and growth factors: toward molecular models for limb development. Cell. 1991 Jul 26;66(2):199–217. doi: 10.1016/0092-8674(91)90612-3. [DOI] [PubMed] [Google Scholar]
  37. Wahlberg P., Fex G., Biörklund A., Tropé C., Willén R. Quantitation and localization of cellular retinol-binding protein in squamous-cell carcinomas of the cervix uteri and of the oral cavity. Int J Cancer. 1988 May 15;41(5):771–776. doi: 10.1002/ijc.2910410523. [DOI] [PubMed] [Google Scholar]
  38. Wahlberg P., Fex G., Wennerberg J., Willén R. Cellular retinol-binding protein in mucosa, in benign and malignant non-squamous cell tumours of the head and neck. Acta Otolaryngol. 1989 Mar-Apr;107(3-4):313–320. doi: 10.3109/00016488909127515. [DOI] [PubMed] [Google Scholar]

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