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Mol Biol Rep (2014) 41:81638167 DOI 10.1007/s11033-014-3716-2
Oncogenicity of LHX2 in pancreatic ductal adenocarcinoma
Feng Zhou Shanmiao Gou Jiongxin Xiong
Heshui Wu Chunyou Wang Tao Liu
Received: 29 March 2014 / Accepted: 28 August 2014 / Published online: 17 October 2014 Springer Science+Business Media Dordrecht 2014
Abstract The LIM proteins (Lhx1, Lhx2, Lhx3 and Lhx4) have been report to play important roles in human development. The function role of Lhxs have been characterized in various tumor tissues as cancer suppressors or promoters in different can status and types. The aim of present study was to clarify the function role of Lhx proteins in human pancreatic ductal adenocarcinoma (PDA). The gene expression proles of Lhxs was evaluated using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohisto-chemistry in human PDA tissues compared with normal pancreatic tissues, which identied the gene overexpression of Lhx2 in PDA. Furthermore, we discovered that Lhx2 promoted cancer cell proliferation in vitro/vivo and elevated b-catenin levels correlated with Lhx2 expression in PDA while the Lhx2 simulated b-catenin activation was required for LMO1s oncogenic effects. Mechanistically, Lhx2 facilitate TCF4 to bind to b-catenin and form a stable
Lhx2/TCF4/b-catenin complex and trans-active its downstream target gene. Lhx2 mutations that disrupt the Lhx2-b-catenin interaction partially prevent its function in tumor cells.
Keywords Lhx2 Oncogene PDA b-catenin
Introduction
The pancreatic ductal adenocarcinoma (PDA) are characterized as early and aggressive local invasion late clinical presentation, strong resistance to chemotherapy and radiation therapy, metastatic potential, and, a very poor overall prognosis [1]. After diagnosis, the median survival time is only 35 months. To data, the median survival time can be improve to 1020 months by surgical resection improves, however, surgery are amenable to only 20 % of patients with PDA [2]. Recently, different levels of molecular studies, from the level of individual genes/proteins to high throughput gene expression analyses employing modern array technology have been applied in the ask for a better understanding the biology of this kind of cancer and aim to nd new biomarkers and therapeutic targets [3, 4].
LIM homeobox (Lhx) genes play signicant role in the regulating of the developmental processes at several levels: the human tissue patterning in brain, numbers of cell fate specication, and growth [5].
These genes have highly similar...