Cytoplasmic expression of p33ING1b is correlated with tumorigenesis and progression of human esophageal squamous cell carcinoma

Zhu,Zhen-Long; Yan,Bao-Yong; Zhang,Yu; Yang,Yan-Hong; Wang,Zheng-Min; Zhang,Hong-Zhen; Wang,Ming-Wei; Zhang,Xiang-Hong; Sun,Xiao-Feng

doi:10.3892/ol.2012.983

Cytoplasmic expression of p33ING1b is correlated with tumorigenesis and progression of human esophageal squamous cell carcinoma

Authors:
- Zhen-Long Zhu
- Bao-Yong Yan
- Yu Zhang
- Yan-Hong Yang
- Zheng-Min Wang
- Hong-Zhen Zhang
- Ming-Wei Wang
- Xiang-Hong Zhang
- Xiao-Feng Sun
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Affiliations: Department of Pathology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China, Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China, Clinical College of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China, Graduate School of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Country Council of Östergötland, University of Linköping, Linköping, Sweden
Published online on: October 22, 2012 https://doi.org/10.3892/ol.2012.983
Pages: 161-166

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Abstract

p33ING1b, a newly discovered candidate tumor suppressor gene and a nuclear protein, belongs to the inhibitor of growth gene family. Previous studies have shown that p33ING1b is involved in the restriction of cell growth and proliferation, apoptosis, tumor anchorage-independent growth, cellular senescence, maintenance of genomic stability and modulation of cell cycle checkpoints. Loss of nuclear p33ING1b has been observed in melanoma, seminoma, papillary thyroid carcinoma, oral squamous cell carcinoma, breast ductal cancer and acute lymphoblastic leukemia. Inactivation and/or decreased expression of p33ING1b have been reported in various types of cancer, including head and neck squamous cell, breast, lung, stomach, blood and brain malignancies. Since little is known about the clinicopathological significance of p33ING1b in esophageal squamous cell carcinoma (ESCC), this study aimed to investigate the association of p33ING1b expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in patients with ESCC. p33ING1b expression was examined by immunohistochemistry in 20 normal esophageal mucosa and in 64 ESCC specimens. The results revealed that the positive expression of p33ING1b protein in normal squamous cells was localized in the nucleus alone and the positive rate was 95%, while in ESCCs, the positive expression was mainly in the cytoplasm, together with nuclear expression, and the positive rate was 36% (P<0.0001). Furthermore, the cases with lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P=0.001). The cytoplasmic expression of p33ING1b was positively related to PINCH expression (P<0.0001) in ESCC, and the cases positive for both proteins had a high lymph node metastasis rate (P=0.001). In conclusion, p33ING1b cellular compartmental shift from the nucleus to the cytoplasm may cause loss of normal cellular function and play a central role in the tumorigenesis and metastasis of ESCC.

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