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

Abstract

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 p33 ING1b 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 p33 ING1b 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.

Alteration in the subcellular location of the inhibitor of growth proteinp33(ING1b) in estrogen receptor alpha positive breast carcinoma cells

“…Furthermore, it has been shown that the transfer of p33(ING1b) protein from the nucleus to the cytoplasm may result in the loss of normal cellular function of the protein. This might play a role in tumorigenesis and lymph node metastasis of oral squamous cell carcinomas as well as esophageal squamous cell carcinoma (Zhang et al, 2008;Zhu et al, 2012). Several studies showed that nuclear import of p33(ING1b) occurs concomitantly with physical and/or functional interactions with a subset of nuclear proteins, including p53, p300/CBP, and HDAC1 in different models.…”