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PI 3K is required for both basal and LPA ‐induced DNA synthesis in oral carcinoma cells
Author(s) -
Aasrum Monica,
Tjomsland Vegard,
Thoresen G. Hege,
De Angelis Paula M.,
Christoffersen Thoralf,
Brusevold Ingvild J.
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12384
Subject(s) - transactivation , pi3k/akt/mtor pathway , cell growth , protein kinase b , mapk/erk pathway , microbiology and biotechnology , cell culture , biology , chemistry , signal transduction , biochemistry , transcription factor , genetics , gene
Background The glycerophospholipid lysophosphatidic acid ( LPA ), which is present in most tissues and in high concentrations in saliva, may exert profound effects on oral cancer cells. We have investigated mitogenic signalling induced by LPA in the two oral carcinoma cell lines, D2 and E10, focusing on the role of EGFR transactivation and downstream pathways. Methods Two oral squamous carcinoma cell lines, D2 and E10, were analysed for effects of LPA on signalling pathways and induction of DNA synthesis. Pathway activation was investigated by examining phosphorylation of signalling proteins and by the use of specific pathway inhibitors. Results The D2 cells had higher levels of activated signalling proteins and higher DNA synthesis activity in the basal condition than E10 cells. EGF did not induce proliferation in D2 cells, whereas LPA induced proliferation in both cell lines, by mechanisms depending on EGFR transactivation. Release of EGFR ligands was involved in basal and LPA ‐induced proliferation in both D2 and E10 cells. The proliferation in D2 cells was dependent on the PI 3K/Akt pathway, but not the MEK / ERK pathway. In E10 cells, the PI 3K/Akt, MEK / ERK and p38 pathways were all involved in the proliferation. Conclusion Transactivation of EGFR is required for LPA ‐induced DNA synthesis in D2 and E10 cells. Our results also show that although proliferation of oral carcinoma cells is regulated by several pathways, and differentially in E10 and D2 cells, the PI 3K pathway has a crucial role in both cell lines.