TY - JOUR
T1 - Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug-resistance phenotype in multiple myeloma
AU - Inoue, Jun
AU - Otsuki, Takemi
AU - Hirasawa, Akira
AU - Imoto, Issei
AU - Matsuo, Yoshinobu
AU - Shimizu, Shiroh
AU - Taniwaki, Masafumi
AU - Inazawa, Johji
N1 - Funding Information:
Supported by Grants-in-Aid for Scientific Research (B) and Scientific Research on Priority Areas (C) from the Ministry of Education, Culture, Sports, Science, and Technology; Core Research for Evolutional Science and Technology; Japan Science and Technology Corporation; and the Center of Excellence program for Frontier Research on Molecular Destruction and Reconstitution of Tooth and Bone.
PY - 2004/7
Y1 - 2004/7
N2 - We investigated DNA copy number aberrations in 37 cell lines derived from multiple myelomas (MMs) using comparative genomic hybridization, and 11 (29.70%) showed high-level gain indicative of gene amplification at 1q12-q22. A corresponding transcriptional mapping using oligonucleotide arrays extracted three up-regulated genes (IRTA2, PDZK1, and S100A6) within the smallest region of overlapping in amplifications. Among them PDZK1 showed amplification and consequent overexpression in the MM cell lines. Amplification of PDZK1 was observed in primary cases of MM as well. MM cell lines with amplification of PDZK1 exhibited the resistance to melphalan-, cis-platin-, and vincristin-induced cell death compared with MM cell lines without its amplifications. Furthermore, down-regulation of PDZK1 with an anti-sense oligonucleotide sensitized a cell line KMS-11 to melphalan, cis-platin, and vincristin. Taken together, our results indicate that PDZK1 is likely to be one of targets for 1q12-q22 amplification in MM and may be associated with the malignant phenotype, including drug resistance, in this type of tumor.
AB - We investigated DNA copy number aberrations in 37 cell lines derived from multiple myelomas (MMs) using comparative genomic hybridization, and 11 (29.70%) showed high-level gain indicative of gene amplification at 1q12-q22. A corresponding transcriptional mapping using oligonucleotide arrays extracted three up-regulated genes (IRTA2, PDZK1, and S100A6) within the smallest region of overlapping in amplifications. Among them PDZK1 showed amplification and consequent overexpression in the MM cell lines. Amplification of PDZK1 was observed in primary cases of MM as well. MM cell lines with amplification of PDZK1 exhibited the resistance to melphalan-, cis-platin-, and vincristin-induced cell death compared with MM cell lines without its amplifications. Furthermore, down-regulation of PDZK1 with an anti-sense oligonucleotide sensitized a cell line KMS-11 to melphalan, cis-platin, and vincristin. Taken together, our results indicate that PDZK1 is likely to be one of targets for 1q12-q22 amplification in MM and may be associated with the malignant phenotype, including drug resistance, in this type of tumor.
UR - http://www.scopus.com/inward/record.url?scp=3042683879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042683879&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)63276-2
DO - 10.1016/S0002-9440(10)63276-2
M3 - Article
C2 - 15215163
AN - SCOPUS:3042683879
SN - 0002-9440
VL - 165
SP - 71
EP - 81
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -