TY - JOUR
T1 - FAK overexpression upregulates cyclin D3 and enhances cell proliferation via the PKC and PI3-kinase-Akt pathways
AU - Yamamoto, Daisuke
AU - Sonoda, Yoshiko
AU - Hasegawa, Maki
AU - Funakoshi-Tago, Megumi
AU - Aizu-Yokota, Eriko
AU - Kasahara, Tadashi
N1 - Funding Information:
This work was supported by the grants from the Ministry of Education, Culture and Science of Japan (No. 12672118 and 13672398).
PY - 2003/6/1
Y1 - 2003/6/1
N2 - We previously demonstrated that FAK-transfected HL-60 (HL-60/FAK) cells exhibit anti-apoptotic capacity. Here, we report that HL-60/FAK cells proliferate much faster than vector-transfected control (HL-60/Vect) cells with a 1.5-fold faster doubling time. This observation prompted us to investigate the mechanism of how HL-60/FAK cells augment cell proliferation. Since a protein kinase C (PKC) inhibitor, chelerythrine, or a PI3-kinase inhibitor, LY294002, suppressed cell proliferation effectively, both PKC and PI-3-kinase pathways are presumed to be involved in the cell proliferation. Among cyclins and CDKs, cyclin D3 expression was particularly prominent in the HL-60/FAK cells. Among PKC family, particularly PKCα, β and η isoforms were activated and directly associated with FAK in HL-60/FAK cells. We assumed that FAK activates PKC and PI3-kinase-Akt pathway, which resulted in marked induction of cyclin D3 expression and CDK activity.
AB - We previously demonstrated that FAK-transfected HL-60 (HL-60/FAK) cells exhibit anti-apoptotic capacity. Here, we report that HL-60/FAK cells proliferate much faster than vector-transfected control (HL-60/Vect) cells with a 1.5-fold faster doubling time. This observation prompted us to investigate the mechanism of how HL-60/FAK cells augment cell proliferation. Since a protein kinase C (PKC) inhibitor, chelerythrine, or a PI3-kinase inhibitor, LY294002, suppressed cell proliferation effectively, both PKC and PI-3-kinase pathways are presumed to be involved in the cell proliferation. Among cyclins and CDKs, cyclin D3 expression was particularly prominent in the HL-60/FAK cells. Among PKC family, particularly PKCα, β and η isoforms were activated and directly associated with FAK in HL-60/FAK cells. We assumed that FAK activates PKC and PI3-kinase-Akt pathway, which resulted in marked induction of cyclin D3 expression and CDK activity.
KW - Akt
KW - Cell proliferation
KW - Cyclin D3
KW - Focal adhesion kinase
KW - PKC
KW - Phosphatidylinositol 3-kinase
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U2 - 10.1016/S0898-6568(02)00142-0
DO - 10.1016/S0898-6568(02)00142-0
M3 - Article
C2 - 12681445
AN - SCOPUS:0037409464
SN - 0898-6568
VL - 15
SP - 575
EP - 583
JO - Cellular Signalling
JF - Cellular Signalling
IS - 6
ER -