Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human lung cancer

Abstract

The ING1 gene is involved in the regulation of the cell cycle, senescence, and apoptosis and is a novel candidate tumor suppressor gene. ING2, another gene in the ING family, was identified and cloned. The functions of ING1 and ING2 largely depend on the activity of p53. To determine whether an alteration in these genes plays a role in carcinogenesis and tumor progression in lung cancer, we screened 30 human lung cancer cell lines and 31 primary lung cancer tumors for mutations in these genes using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing. Our findings failed to uncover any mutations in these genes. We also examined the expression of ING1 and ING2 in lung cancer cell lines that either had or lacked a p53 mutation, and in a control bronchial epithelium cell line, using quantitative real-time reverse transcriptionpolymerase chain reaction (RT-PCR). ING1 expression was up-regulated in all 7 lung cancer cell lines that had a p53 mutation, while the expression of ING2 was down-regulated in 6 of 7 lung cancer cell lines that had a p53 mutation. These results suggest that the ING1 and ING2 genes have different roles in lung carcinogenesis and progression, and the ING2 gene may be an independent tumor suppressor candidate on p53.

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).…”

Nuclear ING2 expression is reduced in human cutaneous melanomas

“…Using the tissue microarray technology and immunohistochemistry, we for the first time demonstrated that ING2 nuclear expression is reduced in human melanomas compared to dysplastic nevi ( There is only one recent report by Okano et al (2006) showing that ING2 expression is reduced in six of seven lung cancer cell lines. However, these authors did not detect any ING2 mutation in 31 human lung cancer cell lines and 30 lung cancer biopsies.…”

Role of ING Family Tumor Suppressors in Breast Cancer

“…Recently reduced expression of ING2 mRNA as well as protein was observed in hepatocellular carcinoma (HCC) [95]. Decreased ING2 expression (but not ING2 mutation) has been observed in lung cancer [96]. Decrease of nuclear ING2 protein was observed in melanoma [57].…”