Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non‐Hodgkin's lymphoma

Abstract

Summary. Non‐Hodgkin's lymphoma (NHL) has a wide biological heterogeneity and shows extremely variable responses to therapeutic measures. However, markers that indicate disease activity and determine treatment strategies for this malignancy are little recognized. Using the differential display method, we have identified Aurora2/BTAK/STK15, a centrosome‐associated serine/threonine kinase, whose overexpression leads to centrosome amplification, chromosomal instability and transformation of mammalian solid tumours. Northern analysis with mRNA from a single tumour cell suspension of NHL confirmed that Aurora2/BTAK/STK15 was highly expressed in histologically aggressive types. To elucidate the function of Aurora2/BTAK/STK15 in NHL, Aurora2/BTAK/STK15 sense or antisense genes were transfected to B‐cell lymphoma cell lines to generate overexpressed or under‐regulated tumour cells. Aurora2/BTAK/STK15 antisense transfectant was barely established compared with a sense or vector‐only transfectant. Two clones were finally established that exhibited a low proliferation rate and significantly increased G1 arrest compared with vector‐only transfectants. Moreover, antisense oligo treatment in vitro showed that restriction of cell growth appeared in proportion to antisense oligo concentration. These results suggest that Aurora2/BTAK/STK15 is an effective candidate to indicate not only disease activity but also tumorigenesis of non‐Hodgkin's lymphoma. Retardation of tumour cell growth resulting from the restriction of this gene's functions may be a novel therapeutic approach for non‐Hodgkin's lymphoma.

Overexpression of Aurora-A Contributes to Malignant Development of Human Esophageal Squamous Cell Carcinoma

“…Expression of Aurora-A can up-regulate telomerase activity and thus promote cell transformation (27). Importantly, amplification and overexpression of Aurora-A have been found in several types of human tumors, including breast cancer (28), hepatocellular cancer (29), bladder cancer (30), testicular germ cell tumors (31), non-Hodgkin's lymphoma (32), and pancreatic cancer (33), although the exact roles of Aurora-A in the development of those tumors are currently under further investigation.…”

Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells

“…Centrosomes in Aurora A-depleted HeLa cells remained immature (Hirota et al, 2003). Elevated levels of Aurora A have been described in human cancers (Zhou et al, 1998;Sen et al, 2002;Ewart-Toland et al, 2003;Gritsko et al, 2003;Hamada et al, 2003;Li et al, 2003). Aurora A overexpression induces resistance to the chemotherapeutic agent paclitaxel by overriding the spindle checkpoint (Anand et al, 2003).…”

Aurora kinase A-specific T-cell receptor gene transfer redirects T lymphocytes to display effective antileukemia reactivity

“…13 Furthermore, we found that AURKA mRNA is overexpressed in a large proportion of freshly isolated human leukemia cells. 6 However, in normal tissues, AURKA mRNA expression is largely limited to the testis.…”

“…We have previously shown that testis is the only tissue that expresses detectable levels of AURKA, which suggests that this antigen behaves like cancer/testis antigens. 13 Based on these findings, we previously studied the immunotherapeutic potential of AURKA and identified an HLA-A*0201-restricted antigenic nonamer epitope derived from the kinase domain (residues 207-215). The AURKA 207-215 epitope (YLILEYAPL) was recognized by CD8 ϩ cytotoxic T lymphocytes (CTLs) generated in vitro.…”