This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guo, X. Articles by Gudas, L. J. Search for Related Content PubMed PubMed Citation Articles by Guo, X. Articles by Gudas, L. J.

Metabolism of all-trans-Retinol in Normal Human Cell Strains and Squamous Cell Carcinoma (SCC) Lines from the Oral Cavity and Skin: Reduced Esterification of Retinol in SCC Lines¹

Department of Pharmacology, Cornell University Medical College, New York, New York 10021

Retinoids, metabolites and synthetic derivatives of vitamin A (retinol), have been shown to inhibit carcinogenesis in various epithelial tissues in animal model systems and to have clinical efficacy as chemotherapeutic agents against certain types of cancer, including squamous cell carcinomas (SCCs). We examined the metabolism of [³H]retinol in normal human cell strains and SCC lines from the oral cavity and skin, and we report here that the cultured normal human epithelial cell strains esterified [³H]retinol to a much greater extent than the SCC lines. Furthermore, microsomal extracts of normal cell strains (e.g., OKF4) exhibited about 7-fold more palmityl-CoA-dependent, phenylmethylsulfonyl fluoride-resistant retinol esterification activity than extracts from SCC lines (e.g., SCC25). The fact that the esterification of retinol was phenylmethylsulfonyl fluoride resistant suggests that the enzyme acyl-CoA:retinol acyltransferase is involved. Culture of both the normal and SCC lines in the presence of 1 µM all-trans-retinoic acid (RA) for 48 h enhanced the formation of [³H]retinyl esters from [³H]retinol. All of the cell lines examined can also metabolize [³H]retinol to [³H]RA, [³H]14-hydroxy-4,14-retroretinol, [³H]retinaldehyde, and [³H]3,4-didehydroretinol, but this metabolism occurs to varying extents in different cell lines. Culture of the cells in the presence of RA for 48 h did not affect the subsequent metabolism of [³H]retinol to [³H]RA and [³H]14-hydroxy-4,14-retroretinol, but it did reduce the metabolism of [³H]retinol to [³H]3,4-didehydroretinol. When cultured for 6–10 h in the presence of nanomolar concentrations of exogenous [³H]retinol, both the normal and SCC lines had much higher intracellular [³H]retinol concentrations, in the micromolar range. No correlation was seen between CRABP II or CRBP I mRNA levels and the levels of either intracellular [³H]retinol or [³H]retinol metabolism in these lines. The reduced ability to esterify retinol in these tumor cells may result in inappropriate cell growth and the loss of normal differentiation responses because of the lack of a sufficient amount of internal retinol stored as retinyl esters.

¹ This work was supported by NIH Grants R01CA43796 and DE10389 (to L. J. G.) and in part by NIH Fellowship 1F32DE05666 (to X. G.).

² To whom requests for reprints should be addressed, at Department of Pharmacology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021. Phone: (212) 746-6250; Fax: (212) 746-8858.

Received 7/21/97. Accepted 10/23/97.

This article has been cited by other articles:

				I. Nazarenko, R. Schafer, and C. Sers Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells J. Cell Sci., April 15, 2007; 120(8): 1393 - 1404. [Abstract] [Full Text] [PDF]

				X.-H. Tang, M.-J. Suh, R. Li, and L. J. Gudas Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid J. Lipid Res., January 1, 2007; 48(1): 165 - 176. [Abstract] [Full Text] [PDF]

				L. Liu and L. J. Gudas Disruption of the Lecithin:Retinol Acyltransferase Gene Makes Mice More Susceptible to Vitamin A Deficiency J. Biol. Chem., December 2, 2005; 280(48): 40226 - 40234. [Abstract] [Full Text] [PDF]

				E. Y. Park, A. Dillard, E. A. Williams, E. T. Wilder, M. R. Pepper, and M. A. Lane Retinol Inhibits the Growth of All-Trans-Retinoic Acid-Sensitive and All-Trans-Retinoic Acid-Resistant Colon Cancer Cells through a Retinoic Acid Receptor-Independent Mechanism Cancer Res., November 1, 2005; 65(21): 9923 - 9933. [Abstract] [Full Text] [PDF]

				S. Boorjian, S. K. Tickoo, N. P. Mongan, H. Yu, D. Bok, R. R. Rando, D. M. Nanus, D. S. Scherr, and L. J. Gudas Reduced Lecithin: Retinol Acyltransferase Expression Correlates with Increased Pathologic Tumor Stage in Bladder Cancer Clin. Cancer Res., May 15, 2004; 10(10): 3429 - 3437. [Abstract] [Full Text] [PDF]

				H. C. Zhan, L. J. Gudas, D. Bok, R. Rando, D. M. Nanus, and S. K. Tickoo Differential Expression of the Enzyme That Esterifies Retinol, Lecithin:Retinol Acyltransferase, in Subtypes of Human Renal Cancer and Normal Kidney Clin. Cancer Res., October 15, 2003; 9(13): 4897 - 4905. [Abstract] [Full Text] [PDF]

				D. P. Simmons, F. Andreola, and L. M. De Luca Human melanomas of fibroblast and epithelial morphology differ widely in their ability to synthesize retinyl esters Carcinogenesis, November 1, 2002; 23(11): 1821 - 1830. [Abstract] [Full Text] [PDF]

				X. Guo, B. S. Knudsen, D. M. Peehl, A. Ruiz, D. Bok, R. R. Rando, J. S. Rhim, D. M. Nanus, and L. J. Gudas Retinol Metabolism and Lecithin:Retinol Acyltransferase Levels Are Reduced in Cultured Human Prostate Cancer Cells and Tissue Specimens Cancer Res., March 1, 2002; 62(6): 1654 - 1661. [Abstract] [Full Text] [PDF]

				F. Cerignoli, X. Guo, B. Cardinali, C. Rinaldi, J. Casaletto, L. Frati, I. Screpanti, L. J. Gudas, A. Gulino, C. J. Thiele, et al. retSDR1, a Short-Chain Retinol Dehydrogenase/Reductase, Is Retinoic Acid-inducible and Frequently Deleted in Human Neuroblastoma Cell Lines Cancer Res., February 1, 2002; 62(4): 1196 - 1204. [Abstract] [Full Text] [PDF]

				M. Sivakumaran, L. M. De Luca, and K. Ozato Role of vitamin A deficiency in the pathogenesis of myeloproliferative disorders Blood, September 1, 2001; 98(5): 1636 - 1637. [Full Text] [PDF]

				I. Klaassen, R. H. Brakenhoff, S. J. Smeets, G. B. Snow, and B. J. M. Braakhuis Enhanced Turnover of all-trans-Retinoic Acid and Increased Formation of Polar Metabolites in Head and Neck Squamous Cell Carcinoma Lines Compared with Normal Oral Keratinocytes Clin. Cancer Res., April 1, 2001; 7(4): 1017 - 1025. [Abstract] [Full Text]

				X. Guo, P. L. Morris, and L. J. Gudas Follicle-Stimulating Hormone and Leukemia Inhibitory Factor Regulate Sertoli Cell Retinol Metabolism Endocrinology, March 1, 2001; 142(3): 1024 - 1032. [Abstract] [Full Text] [PDF]

				X. Guo, D. M Nanus, A. Ruiz, R. R Rando, D. Bok, and L. J Gudas Reduced Levels of Retinyl Esters and Vitamin A in Human Renal Cancers Cancer Res., March 1, 2001; 61(6): 2774 - 2781. [Abstract] [Full Text]

				X. Guo, A. Ruiz, R. R. Rando, D. Bok, and L. J. Gudas Esterification of all-trans-retinol in normal human epithelial cell strains and carcinoma lines from oral cavity, skin and breast: reduced expression of lecithin:retinol acyltransferase in carcinoma lines Carcinogenesis, November 1, 2000; 21(11): 1925 - 1933. [Abstract] [Full Text] [PDF]

				K. C. Lewis and J. F. Hochadel Retinoid Metabolism in the Prostate: Effects of Administration of the Synthetic Retinoid N-(4-Hydroxyphenyl)retinamide Cancer Res., December 1, 1999; 59(23): 5947 - 5955. [Abstract] [Full Text] [PDF]

				M. A. Lane, A. C. Chen, S. D. Roman, F. Derguini, and L. J. Gudas Removal of LIF (leukemia inhibitory factor) results in increased vitamin A (retinol) metabolism to 4-oxoretinol in embryonic stem cells PNAS, November 9, 1999; 96(23): 13524 - 13529. [Abstract] [Full Text] [PDF]