%0 Journal Article
%T Downregulation of Hlx Closely Related to the Decreased Expressions of T-bet and Runx3 in Patients with Gastric Cancer May Be Associated with a Pathological Event Leading to the Imbalance of Th1/Th2
%A Yan Xu
%A Jingjing Gao
%A Zhaoliang Su
%A Xiaoli Dai
%A Yazhen Li
%A Yingzhao Liu
%A Jianguo Chen
%A Jia Tong
%A Yun Zhang
%A Chaoyang Wu
%A Dong Zheng
%A Shengjun Wang
%A Huaxi Xu
%J Journal of Immunology Research
%D 2012
%R 10.1155/2012/949821
%X T-bet plays an important role in immunoregulation; it induces the differentiation of Th1 together with the homeobox transcription factor gene Hlx. Recent studies show that T-bet and Th1-associated factors are critical in regulating tumor development. However, the contributions of Hlx in the occurrence and development of cancer remain unknown. In this study, the Hlx, T-bet, Runx3, and IFN-¦Ã were measured in PBMC from patients with gastric cancer and the correlation between Hlx and T-bet or IFN-¦Ã was assessed. The expression levels of Hlx, T-bet, and IFN-¦Ãwere significantly decreased, and there was a positive correlation between Hlx and T-bet or IFN-¦Ã. In addition, the Runx3 expression was also downregulated with the lower T-bet mRNA level. These results suggested that the decreased Hlx expression was closely associated with T-bet and Runx3 downregulations and may contribute to the development of gastric cancer. 1. Introduction Transcription factors act in concert to induce lineage commitment towards Th1, Th2, Th17, or T regulatory (Treg) cells, and their counter-regulatory mechanisms are shown to be critical for polarization between Th1 and Th2 phenotypes [1¨C3]. Differentiation of naive T lymphocytes into Th1 cell requires IFN-¦Ã (interferon-gamma) which induces the Th1 transcription factor, T-bet. But IFN-¦Ã just induces initial T-bet expression, late expression of T-bet to be needs accompanied by the upregulation of the transcription factors Runx3 and Hlx (also known as Hlx1, H2.0-like homeobox or HB24), and is required to imprint the Th1 cell for IFN-¦Ã reexpression [4]. As a strong candidate for a tumor suppressor, Runx3, a member of runt-related transcription factors (Runx1, Runx2, and Runx3), has been widely studied in a variety of human cancers [5]. Loss of Runx3 leading to elevated oncogenic activity was found to be a key event in inducing a precancerous state of the stomach. The increase in the level of active p53 protein leads to an inhibition of entry into S-phase or the induction of apoptosis [6]. Thus, the loss or inactivation of p53 results in the loss of cell-cycle arrest or apoptosis after DNA damage or physiologic stresses. This loss, seen in many human cancers, has been proposed to lead to increased genetic instability, increased accumulation of mutations, and ultimately oncogenesis. Interestingly, a number of studies indicate that tumor-derived mutant forms of p53, which are highly expressed in many cancers while losing many of their DNA-damage checkpoint functions function as active transforming genes [7]. These mutant p53 genes serve as
%U http://www.hindawi.com/journals/jir/2012/949821/