Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.
Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.
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DOI：
10.1158/1078-0432.ccr-09-0077
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发表时间：
2009-11-01
期刊：
影响因子：
--
通讯作者：
Von Hoff DD
中科院分区：
文献类型：
--
作者：
Warner SL;Stephens BJ;Nwokenkwo S;Hostetter G;Sugeng A;Hidalgo M;Trent JM;Han H;Von Hoff DD
Targeting protein for Xklp2 (TPX2) has gained attention recently as a putative oncogene possibly amplified in several human malignancies including pancreatic adenocarcinoma. In this work, we sought to evaluate the copy number and expression of TPX2 in pancreatic cancer cell lines and tumor tissues and to further explore the potential of TPX2 as a therapeutic target. The DNA copy number and expression of the TPX2 gene were surveyed in pancreatic cancer cell lines and tumor tissues and compared to those of immortalized normal pancreatic ductal cells and normal pancreas tissues. The cellular effects of TPX2 knockdown using siRNA oligonucleotides in pancreatic cancer cells, such as growth in tissue culture, in soft agar, and nude mice, apoptosis and sensitivity to paclitaxel, were also investigated using various assays. Low copy number TPX2 amplification was found in pancreatic cancer cell lines and low passage pancreatic cancer tumor xenografts. TPX2 expression was upregulated in pancreatic cancer cell lines at both the mRNA and protein levels relative to the immortalized pancreatic ductal epithelial cell line HPDE6. Immunohistochemical staining of a tissue microarray showed TPX2 expression was higher in pancreatic tumors compared to their normal counterparts. Treatment with TPX2 targeting siRNAs effectively reduced pancreatic cancer cell growth in tissue culture, induced apoptosis, and inhibited growth in soft agar and in nude mice. Knockdown of TPX2 also sensitized pancreatic cancer cells to paclitaxel treatment. Our results suggest that TPX2 might be an attractive target for pancreatic cancer therapy.
