Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Aug 19;29(1):114.
doi: 10.1186/1756-9966-29-114.

Oncogenic role of the chromobox protein CBX7 in gastric cancer

Xiao-Wei Zhang  1 , Li Zhang, Wei Qin, Xiao-Hong Yao, Lei-Zhen Zheng, Xin Liu, Jin Li, Wei-Jian Guo
Affiliations

Oncogenic role of the chromobox protein CBX7 in gastric cancer

Xiao-Wei Zhang et al. J Exp Clin Cancer Res. .

Abstract

Background: Chromobox 7 (CBX7) is a Polycomb family protein that extends the lifespan of normal human cells via downregulating the expression of INK4a/ARF tumor suppressor locus. It was found that CBX7 expression was upregulated in lymphoma, but downregulated in some other human malignancies. The role of CBX7 in most types of cancer is still not clear. The purpose of this study is to investigate the role of CBX7 in gastric cancer.

Methods: The expression of CBX7 and its potential target protein p16(INK4a) in gastric cancer cell lines and gastric tumors was assayed by Western blot analysis and immunohistochemistry(IHC). The correlations between CBX7 expression and p16(INK4a), clinicopathological characteristics, and prognosis were analyzed. Gastric cancer cell line SGC-7901 was transfected with CBX7 siRNA expressing plasmids, and the expression of various proteins was analyzed by Western blot analysis. Cellular senescence, anchorage independent growth, and cell migration assays were performed to determine the functional role of CBX7 in gastric cancer cells.

Results: CBX7 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of CBX7 in gastric cancer tissues correlated with patients' age, clinical stage and lymph node metastasis. Knockdown of CBX7 expression in gastric cancer cells led to increased cellular senescence, decreased cellular proliferation and migration ability, accompanied by upregulation of p16(INK4a).

Conclusions: CBX7 acts as an oncogene in the carcinogenesis and progression of gastric cancer, and it may regulate tumorigenesis, cell migration and cancer metastasis partially via p16(INK4a) regulatory pathway.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The expression of CBX7 in gastric cancer cell lines and gastric tumors. A) The expression of CBX7 and p16 proteins in an immortalized human normal gastric epithelial cell line GES-1 and various gastric cancer cell lines as detected by Western blot analysis. β-actin was used as a loading control. B) Examples of nuclear staining of CBX7 in normal gastric tissues and gastric cancer tissues by IHC detection: negative CBX7 expression in normal gastric tissue (upper left); negative CBX7 expression (upper right), slight positive CBX7 expression (lower left), and strong CBX7 expression (lower right) in gastric cancer tissues. Tissue sections were stained with CBX7-specific antibody and counterstained with hematoxylin as described in experimental procedures (magnification: ×400).
Figure 2
Figure 2
CBX7 expression in gastric cancer tissues correlated with prognosis in univariate analysis. Kaplan-Meier survival curves were plotted as cumulative survival vs months according to CBX7 expression (negative and positive).
Figure 3
Figure 3
Reduction of transformed phenotype by knockdown of CBX7 expression. A) CBX7 knockdown in SGC-7901 cells resulted in the upregulation of p16 as determined by Western blot analysis. β-actin was used as a loading control. The level of p16 was quantified by densitometric analysis of signal present in each lane and normalizing it to β-actin signal of respective lane using ImageJ 1.37v software (NIH, Bethesda, USA). B) Knockdown of CBX7 expression in SGC-7901 cells resulted in increased cellular senescence (p < 0.01; upper panel, pictures of SA-β-gal stained cells; lower panel, senescent cells were counted and plotted). C) Decreased number of colonies in soft agar in CBX7 knockdown cells (p < 0.01; upper panel, pictures of colonies in soft agar; lower panel, the number of colony were counted and plotted). D) Transwell migration assays using the Corning chamber showed that fewer number of cells migrated in SGC-7901 cells with CBX7 knockdown compared with that in control (p < 0.01; upper panel, pictures of migrated cells; lower panel, the number of migrated cells were counted and plotted).
See this image and copyright information in PMC

References

    1. Gil J, Bernard D, Peters G. Role of polycomb group proteins in stem cell self-renewal and cancer. Dna Cell Biol. 2005;24(2):117–125. doi: 10.1089/dna.2005.24.117. - DOI - PubMed
    1. Qin ZK, Yang JA, Ye YL, Zhang X, Xu LH, Zhou FJ, Han H, Liu ZW, Song LB, Zeng MS. Expression of Bmi-1 is a prognostic marker in bladder cancer. Bmc Cancer. 2009;9:61. doi: 10.1186/1471-2407-9-61. - DOI - PMC - PubMed
    1. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P, Wicha MS. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006;66(12):6063–6071. doi: 10.1158/0008-5472.CAN-06-0054. - DOI - PMC - PubMed
    1. Dimri GP. What has senescence got to do with cancer? Cancer Cell. 2005;7(6):505–512. doi: 10.1016/j.ccr.2005.05.025. - DOI - PMC - PubMed
    1. Mihic-Probst D, Kuster A, Kilgus S, Bode-Lesniewska B, Ingold-Heppner B, Leung C, Storz M, Seifert B, Marino S, Schraml P, Dummer R, Moch H. Consistent expression of the stem cell renewal factor BMI-1 in primary and metastatic melanoma. Int J Cancer. 2007;121(8):1764–1770. doi: 10.1002/ijc.22891. - DOI - PubMed

Publication types

MeSH terms

Substances