Downregulation of Signal Regulatory Protein Alfa 1 in K562 Cells Results in the Aberrant Cell Growth in Low Serum Culture

Signal regulatory protein (SIRP)-α1 is a myeloid inhibitory immunoreceptor. SIRPα1 expression is significantly reduced in the majority of myeloid malignancies. SIRPα1 is a negative regulator of signaling and the reduced expression is considered to play a role in the pathogenesis of these diseases through aberrant signaling, but the biological roles of SIRPα1 remain largely unknown. In this study, by using SIRP-α1-knockdown chronic myeloid leukemia K562 (K562SIRP-α1KD) cells, I found that in low (0.1, 0.3%) serum media, the cell growth was increased until day 5, whereas control cells did not proliferate beyond day 2 under the same serum conditions. Consistently, in K562SIRP-α1KD cells, 2 days of culture in 0.3% serum increased the proportion of S-phase cells, as well as bromodeoxyuridine (BrdU) incorporation compared to their controls. Moreover, serum stimulation experiment revealed that Brd-U positive cells were significantly increased in K562SIRPα1 KD cells. Furthermore, in K562SIRP-α1KD cells, phosphorylation of extracellular regulated kinase (ERK) and Akt was potently increased under low serum conditions. Collectively, these data suggested that down-regulation of SIRPα1 led to the constitutive activation of these aberrant signaling, as well as abnormal growth, in K562 cells.