Abstract
The transcription factor »signal transducer and activator of transcription 5b« (STAT5b) is associated with tumor growth and metastases in various cancer entities (e.g. breast and prostate cancer). Activation of this transcription factor via cytokines (e. g. IL-6), growth factors (e. g. EGF) and oncogenes (e. g. src) promotes growth and motility of tumor cells. Therefore, we sought to determine the expression of STAT5b in human pancreatic adenocarcinoma (HPAC) and investigate the effects of selective STAT5b blockade on tumor growth and motility of pancreatic cancer cell lines. Using immunohistochemistry, expression of nuclear STAT5b was determined in HPAC tissue samples. In vitro, selective inhibition of STAT5b was achieved using stable transfection of human pancreatic cancer cell lines (HPAF-II, L3.6pl, BxPC-3) with STAT5b shRNA plasmid (SureSilencing, Super Array, SA Bioscience). Knock-down of STAT5b was determined using Western Blot. In vitro, the effect of STAT5b blockade on growth of tumor cells was investigated by MTT assays whereas changes in motility were evaluated in Boyden chamber assays. A subcutaneous tumor model was used to determine effects of STAT5b blockade on tumor growth in vivo. Our results show that nuclear expression of STAT5b can be found in 28/31 HPAC tissue samples. In vitro, STAT5b blockade had no effect on growth of tumor cells whereas tumor cell motility was significantly impaired (P < 0.05). The subcutaneous tumor model showed that knock-down of STAT5b leads to significant inhibition of tumor growth (P < 0.05) that was also reflected by final tumor weight (P < 0.05). In summary, STAT5b is expressed in HPAC. Blockade of STAT5b impairs tumor cell motility in vitro and tumor growth in vivo. Hence, STAT5b might be an interesting target for anti-neoplastic therapy in HPAC.
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