Retinoic Acid-dependent Transforming Growth Factor-β2-mediated Induction ofMUC4Mucin Expression in Human Pancreatic Tumor Cells Follows Retinoic Acid Receptor-α Signaling Pathway
作者： Amit Choudhury , Rakesh K Singh , Nicolas Moniaux , Tarek H El-Metwally , Jean-Pierre Aubert
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摘要: The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, Muc4) due to its similar structural organization. Like SMC, may also exist two subunits: a type unit known MUC4α and growth factor-like transmembrane subunit, MUC4β. expression in normal human pancreas not detectable, but it highly expressed pancreatic tumor cells. In present study, we investigated regulation cells CD18/HPAF, exhibiting high level transcripts protein. When these were adapted grow serum-free medium (CD18/HPAF-SF), was undetectable. Among several serum constituents, all-trans-retinoic acid (RA) induced concentration- time-dependent manner. RA-mediated increase transcript coincided with an increased transforming factor-β2 (TGF-β2) transcript. antagonist retinoic receptor (RAR)-α (Ro41–5253) abrogated TGF-β2 by RA. exogenous addition MUC4expression. TGF-β-neutralizing antibody blocked RA-induced well TGF-β2-mediated conclusion, induction MUC4expression carcinoma RA mediated through RAR-α signaling pathway, serve interim mediator this regulated expression.
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