Open AccessEGF effects on p53 in MDA‐468 human breast cancer cells: implications for G 1 arrest
Author(s) -
Prasad K. A. N.,
Church J. G.
Publication year - 1997
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1046/j.1365-2184.1997.00072.x
Subject(s) - downregulation and upregulation , phosphorylation , cell cycle , cell growth , epidermal growth factor , microbiology and biotechnology , biology , cell cycle checkpoint , cell culture , apoptosis , cell , cancer cell , mutant , cancer research , cancer , biochemistry , genetics , gene
EGF, in pharmacological concentrations, inhibits cell proliferation of the MDA‐468 human breast cancer cell line. Previously, we have demonstrated that this was characterized by a reversible cell cycle arrest at the G 1 ‐S boundary, concomitant with downregulation of mRNA levels for p53 (a point mutant, p53 273.His ). Since p53 273.His is regarded as a gain‐of‐function mutant and acts to enhance cell proliferation, we hypothesized that the G 1 arrest induced by EGF might be mediated by p53 273.His . In this study, we report an EGF‐dependent altered conformation as indicated by immunofluorescence, while no significant immediate effects of EGF‐treatment on p53 273.His protein levels and synthesis were observed. These experiments demonstrated a decreased PAb 240 (mutant‐specific) reactivity of nuclear p53 273.His in EGF‐treated cells, while that of PAb 1620 (wild‐type specific) was enhanced. Staining with PAb 1801 (pan specific), on the other hand, showed little change upon EGF treatment. Further studies indicated a decreased phosphorylation of nuclear p53 273 . His in EGF‐treated cells. These EGF‐dependent events were detected early enough to be attributed as causative of cell cycle arrest. We suggest that EGF‐mediated, phosphorylation‐dependent conformational change in nuclear p53 273.His , and in turn altered p53 function, may be responsible for EGF‐dependent growth inhibition MDA‐468 cells.