Suppression of STAT5b in Pancreatic Cancer Cells Leads to Attenuated Gemcitabine Chemoresistance, Adhesion and Invasion

Overview

Journal Oncol Rep

Specialty Oncology

Date 2016 Apr 2

PMID 27035235

Citations 18

Authors

Hiroki Sumiyoshi

Akira Matsushita

Yoshiharu Nakamura

Yoko Matsuda

Toshiyuki Ishiwata

Zenya Naito

Eiji Uchida

Affiliations

Soon will be listed here.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies, and there is an urgent need for new therapeutic strategies based on the molecular biology of PDAC. Signal transducers and activators of transcription 5 (STAT5) are known to be activated in a variety of malignancies and involved in tumor proliferation, apoptosis, and invasion, whereas the expression and biological role of STAT5b in PDAC are less clearly defined. In the present study, we examined the expression and role of STAT5b in human pancreatic cancer cell lines. Expressions of STAT5b mRNA and protein were detected in eight kinds of pancreatic cancer cells. Confocal microscopy and western blot analysis indicated that STAT5b is localized in both cytoplasm and nuclei. Immunoprecipitation analysis revealed tyrosine phosphorylation of STAT5b in pancreatic cancer cells. These results indicate that STAT5b in pancreatic cancer cells is constitutively activated. STAT5b shRNA clones in PANC-1 cells, which express relatively high levels of STAT5b, exhibited reduced chemoresistance against gemcitabine, adhesion and invasion compared to sham. On the other hand, AsPC-1 and BxPC3 cells, which express relatively low levels of STAT5b, exhibited reduced chemoresistance compared to PANC-1 cells. Moreover, STAT5b overexpression clones in AsPC-1 cells exhibited increased chemoresistance compared to sham. STAT5b shRNA clones in PANC-1 cells were more sensitive to the proapoptotic actions of gemcitabine, as evidenced by PARP and cleaved caspase-3 activation. Gemcitabine also significantly reduced Bcl-xL levels in the STAT5b shRNA-expressing cells. We also investigated the clinicopathological characteristics of STAT5b expression of PDAC. Although a significant correlation between STAT5b expression and overall survival rates was not observed, a significant correlation with main pancreatic duct invasion was observed. These findings suggest that STAT5b confers gemcitabine chemoresistance and promotes cell adherence and invasiveness in pancreatic cancer cells. Targeting STAT5b may lead to novel therapeutic strategies for PDAC.

Citing Articles

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Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer.

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PMID: 39000545 PMC: 11242728. DOI: 10.3390/ijms25137438.

STAT5B Suppresses Ferroptosis by Promoting DCAF13 Transcription to Regulate p53/xCT Pathway to Promote Mantle Cell Lymphoma Progression.

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