Nuclear ING2 expression is reduced in human cutaneous melanomas

Abstract

Cutaneous malignant melanoma is a severe and sometimes life-threatening cancer. The molecular mechanism of melanomagenesis is incompletely understood. Deregulation of apoptosis is probably one of the key factors contributing to the progression of melanoma. The inhibitor of growth (ING) family proteins are candidate tumour suppressors which play important roles in apoptosis. Downregulated expression of ING proteins have been reported in several tumour types, including the loss of nuclear expression of p33ING1b in melanoma. As ING2 exhibits 58.9% homology with p33ING1b, we hypothesized that the aberrant expression of ING2 may be involved in melanomagenesis. Here, we used tissue microarray technology and immunohistochemistry to examine ING2 expression in human nevi and melanoma biopsies. Our data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (Po0.05). Our data also revealed that nuclear ING2 expression was not associated with patient's gender, age or tumour thickness, ulceration, American Joint Committee on Cancer (AJCC) stage, tumour subtype, location and 5-year survival (P40.05). Taken together, our results suggest that nuclear ING2 expression is significantly reduced in human melanomas and that reduced ING2 may be an important molecular event in the initiation of melanoma development.

Sumoylation of ING2 regulates the transcription mediated by Sin3A

“…Indeed, ING2 locus is deleted in the head and neck squamous cell carcinomas (Borkosky et al, 2009). In melanoma and in hepatocellular carcinoma a loss of ING2 nuclear expression has been observed (Lu et al, 2006;Zhang et al, 2008). Moreover, we have recently shown a strong decrease of ING2 expression, both at the protein and the mRNA level, in a large proportion of non-small cell lung carcinoma .…”

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

“…ING1 downregulation was observed in different tumor types (breast, gastric, esophageal, blood, lung and brain) (Gong et al, 2005), whereas protein mislocalization was described in tumors of different origin (Nouman et al, 2002). ING2 expression was reduced in colorectal, hepatocellular carcinoma, prostate, pancreatic, lung cancer and cutaneous melanoma (Nagashima et al, 2001;Lu et al, 2006;Okano et al, 2006). Allelic loss and reduced expression of ING3 have been also reported (Gunduz et al, 2002;Nagashima et al, 2003).…”

The tumor suppressor ING3 is degraded by SCFSkp2-mediated ubiquitin–proteasome system

“…Meanwhile, ING1b has been shown to be shifted from the nucleus to the cytoplasm in melanocytic lesions (Nouman et al, 2002), which may be mediated by 14-3-3 proteins (Gong et al, 2006). Both nuclear ING2 and overall ING4 expressions are also downregulated in melanomas, although only the reduced ING4 expression was significantly associated with melanoma progression (Lu et al, 2006;Li et al, 2008). The reduced ING4 expression also correlated with tumor thickness, ulceration and a poorer 5-year patient survival with primary melanomas .…”