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Variants of 3T3 cells lacking mitogenic response to the tumor promoter tetradecanoyl‐phorbol‐acetate
Author(s) -
ButlerGralla Edith,
Herschman Harvey R.
Publication year - 1981
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041070108
Subject(s) - 3t3 cells , biology , epidermal growth factor , cell culture , cell cycle , microbiology and biotechnology , cell growth , phorbol , dna synthesis , growth factor , cell , in vitro , signal transduction , transfection , receptor , biochemistry , genetics , protein kinase c
The potent tumor promoter 12‐ O ‐tetradecanoyl‐phorbol‐13‐acetate (TPA) can stimulate quiescent, nonproliferating 3T3 cells to reenter the cell cycle and divide. We have previously used a slection technique developed in our laboratory to isolate variant cell lines which no longer divide in response to epidermal growth factor. We have now utilized the same selection procedure to isolate, from 3T3 cells, two variant cell lines, TNR‐2 and TNR‐9, which retain growth control and divide in response to elevated serum or fibroblast growth factor, but which do not respond to TPA. The variants do not incorporate precursors into DNA in response to TPA, demonstrating that the cells do not enter the S phase of the cell cycle. The TPA nonresponsive variant TNR‐2 cannot respond to epidermal growth factor; TNR‐9 responds to this mitogen. TNR‐2 variant cells, which do not respond to EGF, do not bind 125 I‐EGF. TPA can modulate 125 I‐EGF binding to TNR‐9 cells in a manner similar to its action on parental 3T3 cells. This TPA‐induced alteration of EGF binding indicates that TNR‐9 cells still interact with TPA, despite their inability to mount a mitogenic response.