In humans embryonal-carcinoma cells

Simeone, A., Acampora, D., Arcioni, L., Andrews, P. W., Boncinelli, E., and Mavilio, F. (1990). Sequential activation of HOX 2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 346 763-766. 

Willert, J., Epping, M., Polack, J.R., Brown, P.O., Nusse, R.A. 2002. A transcriptional response to Wnt protein in human embryonic carcinoma cells. Dev. Biol. 2, 8. 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Gonczol E, Andrews PW, Plotkin SA (1984) Cytomegalovirus replicates in differentiated but not inundiffer-entiated human embryonal carcinoma cells. Science 224 159-161... 

The implementation of animal test protocols in the 1980s has been accompanied by the development of a host of alternative methods to study adverse effects of chemicals on reproductive and developmental parameters. For example, rat whole embryo culture stems from the seventies (16), as does the rat limb bud organ culture (17) and rat limb bud and brain micromass was developed in the eighties (18). An elegant nonvertebrate alternative model used regeneration of polyps of Hydra atUnuata from dissociated cells (19). Animal-free in vitro alternatives include those employing the proliferation of a human embryonic palatal mesenchymal cell line (20), the attachment of a mouse ovarian tumor cell line (21), and the differentiation of a neuroblastoma cell line (22) and a embryonal carcinoma cell line (23). Various overviews of methods have been published over the years (24). The predictability of... 

Przyborski SA, Christie VB, Hayman MW, Stewart R, Horrocks GM (2004) Human embryonal carcinoma stem cells models of embryonic development in humans. Stem Cells Dev 13 400-408... 

Zhang XY, Loflin PT, Gehrke CW, Andrewes P, Ehrlich M. Hypermethylation of human DNA sequences in embryonal carcinoma cells, and somatic tissues, but not in sperm. Nucleic Acids Res. 1987 15 9429-49. 

Fig. 5. Comparison of Northern blot (lanes 1-4) and semiquantitative RT/PCR (lanes 5-8) results. Both methods were used to analyze expression of RARal and RARa2 isoforms in different human cell lines. Note that as expected the expression of RARa2 is induced with RA in T Clu embryonal-carcinoma cells. In this experiment, 30 cycles of PCR have been carried out. Note that RT/PCR is considerably more sensitive (compare lines 1 to 5-8) and generates results which are in agreement with the Northern blot.

Kohler HR, Triebskorn R, Stocker W, Kloetzel PM, Alberti G (1992) The 70 kD heat shock protein in soil invertebrates a possible tool for monitoring environmental toxicants. Arch Environ Contam Toxicol 22 334-338 Kontosoglou TE, Banerjee D, Cherian MG (1989) Immunohistochemical localization of metallothionein in human testicular embryonal carcinoma cells. Virchows Arch [A] 415 545-549... 

In contrast to the murine embryonal carcinoma cells, several human teratocar-cinoma-derived cell lines fail to differentiate when treated with retinoic acid (Matthaei et al., 1983). Yet unlike the mutant murine cells that are refractory to retinoic acid, it has been shown that the human cell lines contain high levels of CRABP. These results and other data presented in the ensuing portions of this chapter make it unclear whether the retinoic acid-CRABP complex plays an obligatory role in the mechanism of promotion of differentiation. 

To the extent that it is possible, we attempt to simplify the picture by discussing separately each of the cellular systems in which evidence exists for retinoid-mediated effects on protein kinases and protein phosphorylation. In studies of the biochemical effects of retinoids we are again faced with the central role occupied by their specific effects on neoplastic cells. The cellular systems employed for these studies have been either murine embryonal carcinoma cells (F9) or human promyelocytic leukemia cells (HL-60), each of which has been demonstrated to undergo terminal differentiation to nonneoplastic cell types following retinoid treatment (see Section IV,B,1 and 2), or murine melanoma cells in which retinoids have a marked antiproliferative effect (Section IV,B,3). 

GlcNAc(pi-6 )]LacNAc(pl-3 )[GlcNAc(pi-6 )]LacNAc, that was converted to the tetradecasaccharide LacNAc(pi-3 )[LacNAc(pl-6 )]LacNAc(pi-3 )-[LacNAc(pi-6 )]LacNAc(pi-3 )[LacNAc(pi-6 )]LacNAc by a treatment with UDP-Gal and P4-GalT I. Branched polylactosamine backbones of this type are expressed in human erythrocytes and embryonic carcinoma cells. 

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