Transcriptional regulation of alpha1,3-galactosyltransferase in embryonal carcinoma cells by retinoic acid. Masking of Lewis X antigens by alpha-galactosylation.
Treatment of mouse teratocarcinoma F9 cells with all-trans-retinoic acid (RA) causes a 9-fold increase in steady-state levels of mRNA for UDP-Gal:beta-D-Gal alpha1,3-galactosyltransferase (alpha1,3GT) beginning at 36 h. Enzyme activity rises in a similar fashion, which also parallels the induction of laminin and type IV collagen. Nuclear run-on assays indicate that this increase in alpha1,3GT in RA-treated F9 cells, like that of type IV collagen, is transcriptionally regulated. Differentiation also results in increased secretion of soluble alpha1,3GT activity into the growth media. The major alpha-galactosylated glycoprotein present in the media of RA-treated F9 cells, but not of untreated cells, was identified as laminin. Differentiation of F9 cells is accompanied by an increase in alpha-galactosylation of membrane glycoproteins and a decrease in expression of the stage-specific embryonic antigen, SSEA-1 (also known as the Lewis X antigen or LeX), which has the structure Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-R. However, flow cytometric analyses with specific antibodies and lectins, following treatment of cells with alpha-galactosidase, demonstrate that differentiated cells contain LeX antigens that are masked by alpha-galactosylation. Thus, RA induces alpha1,3GT at the transcriptional level, resulting in major alterations in the surface phenotype of the cells and masking of LeX antigens.
Cho
S K
SK
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Yeh
J
J
Cho
M
M
Cummings
R D
RD
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D018236:Carcinoma, Embryonal; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006031:Glycosylation; D007700:Kinetics; D007797:Laminin / Q000096:biosynthesis; D016256:Lewis X Antigen / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D011887:Raffinose / Q000494:pharmacology; D018243:Teratocarcinoma; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007797:Laminin; D016256:Lewis X Antigen; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014212:Tretinoin; D003994:Bucladesine; D005700:Galactosyltransferases; C038887:N-acetyllactosamine alpha-D-galactosyltransferase; D011887:Raffinose