Enhanced expression of PCAF endows apoptosis resistance in cisplatin-resistant cells.
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 G(1) 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.
Hirano
Gen
G
Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Izumi
Hiroto
H
Kidani
Akihiko
A
Yasuniwa
Yoshihiro
Y
Han
Bin
B
Kusaba
Hitoshi
H
Akashi
Koichi
K
Kuwano
Michihiko
M
Kohno
Kimitoshi
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*; D050880:p300-CBP Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000099224:p300-CBP-Associated Factor
D000970:Antineoplastic Agents; D002945:Cisplatin; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor