Cytoplasmic expression of p33^ING1b is correlated with tumorigenesis and progression of head and neck squamous cell carcinoma

Xiao-Han Li^1,2, Akira Noguchi³, Takeshi Nishida³, Hiroyuki Takahashi¹, Yang Zheng¹, Xiang-Hong Yang², Shinji Masuda⁴, Keiji Kikuchi¹ and Yasuo Takano<sup>1

1</sup>Kanagawa Cancer Center Research Institute, Yokohama, Japan, ²Division of Pathology, Affiliated Shengjing Hospital of China Medical University, Shenyang, China, ³Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan and ⁴Division of Pathology, Kouseiren Takaoka Hospital, Takaoka, Japan.

Offprint requests to: Yasuo Takano, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan. e-mail: ytakano@gancen.asahi.yokohama.jp


Summary. To clarify the role of p33^ING1b in tumorigenesis and progression of head and neck squamous cell carcinoma (HNSCC), we examined the expression and subcellular localization of p33^ING1b in 214 HNSCC cases in parallel with 60 dysplasia samples and 48 normal epithelium samples by immunohistochemistry, and analyzed correlations of expression of p33^ING1b in HNSCC cases with clinicopathological variables, apototic index and expression of 14-3-3η, p300, p21 and PCNA. Although 12% of HNSCC cases lost expression of p33^ING1b, most cases of HNSCC retained expression of p33^ING1b with levels similar to those in non-cancerous epithelia. Nuclear expression of p33^ING1b was significantly decreased in HNSCC compared to normal epithelia. In contrast, cytoplasmic expression of p33^ING1b was found to be significantly higher in HNSCC. An abundance of p33^ING1b in cytoplasm positively correlated with poor differentiation and tumor progression. Corresponding to those clinicopathogical features, high expression of p33^ING1b in the cytoplasm correlated with PCNA labelling index but in contrast, that in the nuclei correlated with apoptosis. In nuclei, p33^ING1b is coexpressed with p300 and p21, implying its roles in tumor suppression. Elevated expression of 14-3-3η was associated with cytoplasmic expression of p33^ING1b and immunofluorescence study suggested association of p33^ING1b and 14-3-3η. Among three cell lines derived from oral SCC, poorly-differentiated SAS cells showed a relatively high expression of p33^ING1b in cytoplasm with increased level of 14-3-3η. The results obtained here suggest that relocation of p33^ING1b from the nucleus to the cytoplasm, where the protein is tethered by 14-3-3η, participates in tumorigenesis and progression in HNSCC. Histol Histopathol 26, 597-607 (2011)

Key words: p33^ING1b, 14-3-3η, HNSCC, Tumorigenesis

DOI: 10.14670/HH-26.597