Çalışkaner Zihni Onur, Çakar Türkan, Özçelik Emrah, Özdilek Ahmet, Kim Annette S, Doğan Öner, Bosompem Amma, Grosveld Gerard, Saka Bülent, Kandilci Ayten
Department of Molecular Biology and Genetics, Gebze Technical University, Gebze, Kocaeli, Turkey.
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
PLoS One. 2017 May 30;12(5):e0178025. doi: 10.1371/journal.pone.0178025. eCollection 2017.
Overexpression of DEK oncogene is associated with increased proliferation of carcinoma cells and it is observed in several solid tumors due to the amplification of the 6p22.3 chromosomal region where DEK locates. Although the same chromosomal amplification occurs in multiple myeloma (MM), a plasma cell neoplasm, whether the expression and the copy number of the DEK gene are affected in MM remains elusive. We show that despite the increased copy number in CD138positive MM cells (4 out of 41 MM samples), DEK mRNA expression was down-regulated compared with that in CD138negative bone marrow (BM) cells of the same patients (P<0.0001). DEK protein was not detectable by immunohistochemistry (IHC) in CD138positive normal plasma cells or in malignant plasma cells of MM patients (n = 56) whereas it was widely expressed in normal and neoplastic B-cells. Stable knockdown or overexpression of DEK in CD138positive MM cell lines did not affect the proliferation and viability of the cells profoundly in the presence or absence of chemotherapeutic agent melphalan whereas knockdown of DEK moderately but significantly increased the expression level of CD138 (p<0.01). Decreased DEK expression in plasma cells suggests a potential role of this gene in plasma cell development and lack of detectable DEK protein by IHC could be used as a biomarker for normal and malignant plasma cells.
DEK癌基因的过表达与癌细胞增殖增加相关,并且在几种实体瘤中可观察到,这是由于DEK所在的6p22.3染色体区域发生扩增所致。尽管在浆细胞瘤多发性骨髓瘤(MM)中也出现了相同的染色体扩增,但MM中DEK基因的表达和拷贝数是否受到影响仍不清楚。我们发现,尽管CD138阳性MM细胞(41例MM样本中有4例)的拷贝数增加,但与同一患者的CD138阴性骨髓(BM)细胞相比,DEK mRNA表达下调(P<0.0001)。在CD138阳性正常浆细胞或MM患者的恶性浆细胞(n = 56)中,免疫组织化学(IHC)检测不到DEK蛋白,而它在正常和肿瘤性B细胞中广泛表达。在CD138阳性MM细胞系中稳定敲低或过表达DEK,在有或没有化疗药物美法仑的情况下,对细胞的增殖和活力没有显著影响,而敲低DEK可适度但显著增加CD138的表达水平(p<0.01)。浆细胞中DEK表达的降低表明该基因在浆细胞发育中可能起作用,并且通过IHC检测不到DEK蛋白可作为正常和恶性浆细胞的生物标志物。