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• W2023615913 abstract "Human keratinocytes (HKc) immortalized by human papillomavirus type 16 DNA (HKc/HPV16) progress toward malignancy through growth factor-independent (HKc/GFI) and differentiation-resistant stages (HKc/DR). This progression is associated with a loss of sensitivity to growth inhibition by both all-trans-retinoic acid (RA) and transforming growth factor-β (TGF-β). In the accompanying article (Borger et al., 2000, Virology 270, 397–407), we demonstrate that RA resistance in HKc/HPV16 arises despite functional nuclear retinoid receptors and that TGF-β mediates growth inhibition by RA. To investigate the basis for the loss of TGF-β sensitivity during in vitro progression of HKc/HPV16, we explored the expression of TGF-β receptors type I and type II in independently derived HKc/HPV16 lines and their corresponding HKc/GFI and HKc/DR derivatives. While TGF-β receptor type II mRNA levels were unchanged during progression, mRNA levels for TGF-β receptor type I decreased dramatically as the cells became TGF-β resistant. At the HKc/DR stage, loss of TGF-β receptor type I mRNA, compared to low-passage cells, ranged from 55 to 87% in four HKc/HPV16 lines examined. Immunohistochemistry, using anti-TGF-β receptor type I antibodies, confirmed a loss of TGF-β receptor type I expression in HKc/DR. Reintroduction of the TGF-β-receptor type I into TGF-β-resistant HKc/DR completely restored growth inhibition by TGF-β. Southern blot analysis of DNA extracted from normal HKc, HKc/HPV16, and HKc/DR ruled out any gross changes in the TGF-β receptor type I gene. The activity of the TGF-β receptor type I promoter, cloned upstream of a luciferase reporter gene, was decreased in HKc/DR, to an extent comparable to the decrease in mRNA levels for the TGF-β receptor type I. Thus, TGF-β resistance at late stages of HPV16-mediated transformation of HKc is the result of a loss of expression of TGF-β receptor type I." @default.
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• W2023615913 date "2000-05-01" @default.
• W2023615913 modified "2023-10-12" @default.
• W2023615913 title "Loss of Transforming Growth Factor-β (TGF-β) Receptor Type I Mediates TGF-β Resistance in Human Papillomavirus Type 16-Transformed Human Keratinocytes at Late Stages of in Vitro Progression" @default.
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• W2023615913 doi "https://doi.org/10.1006/viro.2000.0283" @default.
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