作者: Jennifer Rubin Grandis , Qing Zeng , David J. Tweardy
DOI: 10.1038/NM0296-237
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摘要: Retinoic acid (RA) has been shown to be effective in eradicating premalignant lesions and preventing second primary malignancies patients cured of squamous cell carcinoma the head neck (SCCHN) clinical trials. The basis for this effect is unclear. We have previously demonstrated that messenger RNA from tumor growth factor-alpha (TGF-alpha) its receptor, epidermal factor (EGFR), unregulated tumors histologically normal mucosal samples with SCCHN compared control mucosa without cancer, implicating ligand-receptor pair an autocrine pathway early molecular pathogenesis disease. In report, we examined hypothesis action RA on upper aerodigestive tract mediated via downregulation steady-state TGF-alpha and/or EGFR mRNA levels. Following exposure all-trans-RA, a series lines 35.4% reduction expression (P = 0.022) 58.5% 0.0027). Nuclear run-on analysis indicated RA-mediated levels was result decreased gene transcription. These results suggest effects may due downmodulation production.