TY - JOUR
T1 - Enhanced expression of PCAF endows apoptosis resistance in cisplatin-resistant cells
AU - Hirano, Gen
AU - Izumi, Hiroto
AU - Kidani, Akihiko
AU - Yasuniwa, Yoshihiro
AU - Han, Bin
AU - Kusaba, Hitoshi
AU - Akashi, Koichi
AU - Kuwano, Michihiko
AU - Kohno, Kimitoshi
PY - 2010/6
Y1 - 2010/6
N2 - Histone acetyltransferase (HAT) regulates transcription. We have previously shown that two HAT genes, Clock and Tip60, are overexpressed, and upregulate glutathione biosynthesis and the expression of DNA repair genes in cisplatin-resistant cells. To better understand the mechanism of HAT-related drug resistance, we investigated the role of another HAT gene, p300/CBP-associated factor (PCAF ), and found that PCAF was also overexpressed in cisplatin-resistant cells and endowed an antiapoptotic phenotype through enhanced E2F1 expression. PCAF-overexpressing cells showed enhanced expression of E2F1 and conferred cell resistance to chemotherapeutic agents. Downregulation of PCAF decreased E2F1 expression and sensitized cells to chemotherapeutic agents. Moreover, knockdown of PCAF induced G1 arrest and apoptosis. These results suggest that PCAF is one of pleiotropic factors for drug resistance and seems to be critical for cancer cell growth.
AB - Histone acetyltransferase (HAT) regulates transcription. We have previously shown that two HAT genes, Clock and Tip60, are overexpressed, and upregulate glutathione biosynthesis and the expression of DNA repair genes in cisplatin-resistant cells. To better understand the mechanism of HAT-related drug resistance, we investigated the role of another HAT gene, p300/CBP-associated factor (PCAF ), and found that PCAF was also overexpressed in cisplatin-resistant cells and endowed an antiapoptotic phenotype through enhanced E2F1 expression. PCAF-overexpressing cells showed enhanced expression of E2F1 and conferred cell resistance to chemotherapeutic agents. Downregulation of PCAF decreased E2F1 expression and sensitized cells to chemotherapeutic agents. Moreover, knockdown of PCAF induced G1 arrest and apoptosis. These results suggest that PCAF is one of pleiotropic factors for drug resistance and seems to be critical for cancer cell growth.
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U2 - 10.1158/1541-7786.MCR-09-0458
DO - 10.1158/1541-7786.MCR-09-0458
M3 - Article
C2 - 20530585
AN - SCOPUS:77953796034
SN - 1541-7786
VL - 8
SP - 864
EP - 872
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 6
ER -
