Involvement of G-patch domain containing 2 overexpression in breast carcinogenesis.
Through analysis of the detailed genome-wide gene expression profiles of 81 breast tumors, we identified a novel gene, G-patch domain containing 2 (GPATCH2), that was overexpressed in the great majority of breast cancer cases. Treatment of breast cancer cells MCF-7 and T47D with siRNA against GPATCH2 effectively suppressed its expression, and resulted in the growth suppression of cancer cells, suggesting its essential role in breast cancer cell growth. We found an interaction of GPATCH2 protein with hPrp43, an RNA-dependent ATPase. Their interaction could significantly enhance the ATPase activity of hPrp43 and induce a growth-promoting effect on mammalian cells. Because northern blot analyses of normal human organs implied GPATCH2 to be a novel cancer/testis antigen, targeting GPATCH2 or inhibition of the interaction between GPATCH2 and hPrp43 could be a promising novel therapeutic strategy of breast cancer.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Meng-Lay
ML
Lin
Chikako
C
Fukukawa
Jae-Hyun
JH
Park
Kie
K
Naito
Kyoko
K
Kijima
Arata
A
Shimo
Masahiko
M
Ajiro
Toshihiko
T
Nishidate
Yusuke
Y
Nakamura
Toyomasa
T
Katagiri
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007668:Kidney / Q000166:cytology; D008297:Male; D013058:Mass Spectrometry; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014162:Transfection
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; C543032:GPATCH2 protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C539469:DHX15 protein, human; D000251:Adenosine Triphosphatases; C027900:RNA-dependent ATPase; D020365:RNA Helicases