ERK1/2 mediates unbalanced growth leading to senescence induced by excess thymidine in human cells

Excess thymidine induces unbalanced growth by delaying DNA replication and subsequently induces senescence in every human cell type. Our previous studies with use of inhibitors suggested that ERK1/2 has a major role in these processes. Here we directly assessed the roles of ERK1 and ERK2 in unbalanced growth induced by excess thymidine. Knockdown of ERK2 and ERK1 by vector-based RNA interference prevented loss of colony forming ability and appearance of senescence markers induced by excess thymidine in HeLa and TIG-7 cells, respectively. Such cells continued growing in the presence of excess thymidine. Double knockdown of ERK1 and ERK2 did not improve the effects of single knockdowns of ERK1 and ERK2 in either cell types. These results demonstrate that ERK1 or ERK2 has a major role in manifestation of unbalanced growth in human cells.

► Excess thymidine induces unbalanced growth and senescence in normal and tumor cells. ► Knockdown of ERK1 suppressed the above phenomena in normal human fibroblasts. ► Knockdown of ERK2 suppressed the above phenomena in HeLa tumor cells. ► Cells with knockdown ERK1 or ERK2 continuously grew in excess thymidine. ► ERK1/2 has dual roles in checkpoint functions in DNA replication and cell swelling.