ONCOLOGY LETTERS 3: 1017-1022, 2012
Abstract. The effects of the interaction between KLF4 and
β-catenin may be significant in human carcinogenesis and
tumor development. This study aimed to determine whether
the expression of KLF4 and β-catenin in gastric cancer tissues
is associated with clinicopathological characteristics. Western
blot analysis and immunohistochemistry were performed to
detect KLF4 and β-catenin expression in tumor and corre-
sponding non-cancerous tissues from 49 patients. The data
revealed that KLF4 expression was significantly reduced
in gastric cancer tissues compared with normal tissues. By
contrast, the expression of the β-catenin protein was signifi-
cantly increased in all tumor tissues, but was not expressed
in distant normal mucosae. The altered expression of the
KLF4 and β-catenin proteins was associated with advanced
tumor stage and gastric cancer. In addition, the expression of
the KLF4 and β-catenin proteins was inversely associated in
moderately differentiated human gastric cancers. This study
showed that β-catenin expression is significantly increased
and KLF4 protein expression is markedly decreased in gastric
cancer tissues, thus showing that the expression of KLF4 is
inversely correlated with that of β-catenin in gastric cancer.
The altered expression of the two proteins is associated with
advanced tumor stage in gastric cancer.
Gastric cancer remains the fourth most common malignancy
and the second leading cause of cancer-related mortality
worldwide, despite a steady decline in incidence over the
past several decades (1). In recent years, the survival rate of
gastric cancer has significantly improved due to advances in
treatments, including surgery, chemotherapy and radiotherapy.
However, approximately 800,000 individuals still succumb
to gastric carcinoma each year worldwide. Clinically, early
gastric cancer is often asymptomatic or causes non-specific
symptoms; when symptoms occur, the cancer has often
reached an advanced stage. This results in the poor short-term
survival rate of gastric cancer patients due to primary tumor
invasion and metastasis (2). Similar to other types of cancer,
tumor invasion and metastasis are serious clinical problems
and are the most notable properties of aggressive gastric carci-
noma. Gastric cancer development is often associated with a
number of molecular abnormalities, including the inactivation
of various tumor suppressor genes and/or activation of various
oncogenes (3,4). A number of these genes have been investi-
gated as biological markers for the prediction of gastric cancer
staging and lymph node metastasis, but the potential roles of
these genes in the etiology of gastric cancer remain poorly
understood. Investigations into the molecular alterations in
gastric cancer may provide novel insights into the mechanisms
responsible for stomach carcinogenesis and lead to the devel-
opment of biomarkers for the early detection of gastric cancer
and the prediction of its prognosis.
Krüppel-like factor 4, (KLF4) is a newly identified
zinc-finger transcription factor (5). Similar to all Krüppel-like
factors, KLF4 has three zinc-finger domains in its C-terminus
and is involved in various cell and developmental processes,
including cell terminal differentiation and carcinogenesis (6).
The results of previous studies have shown that the expres-
sion level of KLF4 is high in the epithelial cells of the skin,
lung and gastrointestinal tract and is particularly elevated in
terminally differentiated and postmitotic epithelial cells (7).
Other studies have found that KLF4 expression is associ-
ated with the growth arrest of cultured cells (8) and KLF4
overexpression reduces colorectal cancer colony formation,
migration and invasion. By contrast, a decrease or loss of
KLF4 expression frequently occurs in various types of cancer,
including cancers of the colorectum (9,10), stomach (11),
esophagus (12), prostate (13) and lung (14). The expression
levels of KLF4 were found to be inversely associated with
the size of intestinal adenoma in animal experiments (11). In
addition, the results of studies have shown that a decreased
KLF4 expression is associated with poor survival and it is
used as an independent prognostic marker in primary gastric
Altered expression of Krüppel-like factor 4
and β-catenin in human gastric cancer
N. ZHANG*, J. ZHANG*, Z.W. WANG, L. ZHA and Z. HUANG
Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University,
Chongqing 400016, P.R. China
Received December 10, 2011; Accepted February 10, 2012
Correspondence to: Dr Zi-Wei Wang, Department of General
Surgery, The First Affiliated Hospital, Chongqing Medical
University, No. 1 Youyi Rd., Yuzhong District, Chongqing 400016,
Key words: Krüppel-like factor 4, β-catenin, immunohistochemistry,
tumor cell differentiation
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