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TNF accelerates the S‐phase of the cell cycle in tumor cells
Author(s) -
Volland Sabine,
Amtmann Eberhard,
Sauer Gerhard
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560515
Subject(s) - tumor necrosis factor alpha , cancer research , tumor cells , cell cycle , medicine , chemistry , cancer
The reduction of glucose supply induced the killing of tumor cells by tumor necrosis factor (TNF) in vivo and in vitro. In contrast, normal cell lines were resistant to TNF regardless of the presence or absence of glucose. Epidermal growth factor (EGF) did not exert a cytotoxic effect on tumor cells in the absence of glucose. Therefore, the killing mechanism of TNF under conditions of reduced glucose supply was investigated. Flow cytometry experiments and studies of kinetics revealed that the S‐phase of the cell cycle was prolonged in the absence of glucose. After TNF treatment, the S‐phase was found to be shortened and the rate of H‐thymidine incorporation into DNA was increased, whereas EGF failed to exert such an effect. DNA synthesis and entry into mitosis are known to be regulated by cyclin A. In serum‐starved tumor cells (HeLa) we have observed increased cyclin A synthesis within 10 hr, in parallel with enhancement of DNA synthesis and shortening of the S‐phase after TNF treatment. We conclude that, under conditions of low glucose supply, TNF can assume the role of a growth factor in transformed cells.