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Differential effect of tumor necrosis factor on proliferation of primary human keratinocytes and cell lines containing human papillomavirus types 16 and 18
Author(s) -
Villa Luisa Lina,
Vieira Katia Brito Lins,
Pei XuFang,
Schlegel Richard
Publication year - 1992
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940060103
Subject(s) - biology , immortalised cell line , tumor necrosis factor alpha , transforming growth factor , cell culture , cytokine , foreskin , cancer research , keratinocyte , microbiology and biotechnology , immunology , genetics
Keratinocytes immortalized by human papillomaviruses (HPV) 16 and 18 are partially resistant to the inhibition of proliferation exerted by transforming growth factor‐β (TGF‐β). To determine if this finding reflects a generalized resistance to inhibitory cytokines, we studied the effect of tumor necrosis factor‐α (TNF‐α) on subconfluent cultures of both normal and HPV‐immortalized human foreskin keratinocytes. Whereas primary and HPV‐16‐immortalized keratinocytes were sensitive to TNF‐α, HPV‐18‐immortalized keratinocytes (and those immortalized by simian virus 40) were resistant to the inhibitory effects of this cytokine. The ability of HPV‐18 to induce a more resistant phenotype correlated with its more potent in vitro transforming activity and its apparent association with more aggressive tumors. Interestingly, the state of TNF‐induced growth inhibition in normal or HPV‐16—immortalized keratinocytes was not accompanied by a reduction in the expression of c‐myc RNA or protein. This contrasts sharply with the ability of TGF‐β to inhibit c‐myc RNA expression in normal cells. Evidently, the resistance of HPV‐immortalized keratinocytes to TNF‐β and TGF‐β proceeds along different regulatory pathways. © 1992 Wiley‐Liss, Inc.