NOL7 is a nucleolar candidate tumor suppressor gene in cervical cancer that modulates the angiogenic phenotype

Abstract

Cervical cancer is associated with human papilloma virus infection. However, this infection is insufficient to induce transformation and progression. Loss of heterozygosity analyses suggest the presence of a tumor suppressor gene (TSG) on chromosome 6p21.3-p25. Here we report the cloning NOL7, its mapping to chromosome band 6p23, and localization of the protein to the nucleolus. Fluorescence in situ hybridization analysis demonstrated an allelic loss of an NOL7 in cultured tumor cells and human tumor samples. Transfection of NOL7 into cervical carcinoma cells inhibited their growth in mouse xenografts, confirming its in vivo tumor suppressor activity. The induction of tumor dormancy correlated with an angiogenic switch caused by a decreased production of vascular endothelial growth factor and an increase in the production of the angiogenesis inhibitor thrombospondin-1. These data suggest that NOL7 may function as a TSG in part by modulating the expression of the angiogenic phenotype.

Identification of Novel Methylation Markers in Cervical Cancer Using Restriction Landmark Genomic Scanning

“…Increasingly, however, there is evidence demonstrating that such nucleolar proteins, once considered to function solely for ribosomal transcription and subunit assembly, also possess important roles in cell cycle and apoptosis (33,34). Recently, the nucleolar protein NOL7 has been linked as a tumor suppressor gene for cervical cancer (35). Specifically, Hasina et al (35) provided both in vitro and in vivo evidence that NOL7 plays a critical role in the apoptotic index of cervical cancer cells specific to the angiogenic switch, whereby vascular endothelial growth factor production is decreased and angiogenesis inhibitor thrombospondin-1 production is increased.…”

Screening of microsatellite markers in penile cancer reveals differences between metastatic and nonmetastatic carcinomas

“…LOH in microsatellite loci D6S260 and D6S1267 is in this study frequently associated with occurrence of metastases and poor prognosis. As the corresponding 6p22-23 region is known as possible locus of newly discovered metastasis suppressor gene NOL7 in cervical carcinomas, 27 this region could be useful as a prognostic marker in penile carcinomas. Further studies to determine the impact of NOL7 in penile carcinomas are in preparation.…”

The dynamics of the alternatively spliced NOL7 gene products and role in nucleolar architecture

“…24 Expression of NOL7 inhibited the growth of CC cells in mouse xenografts and its effect might be related to the modulation of the angiogenicity of the tumor. The originally published GFP-NOL7 gene-product exhibited nucleolar localization, 22 as expected from proteomic analysis of isolated nucleoli, 12,25 and recently several of its NLS and NoLS sequences were characterized. 26 We characterized 3 alternative transcripts generated from the NOL7 gene and detected the endogenous proteins of the two larger forms.…”

“…A previous study showed that the NOL7 gene can undergo allelic loss in certain cervical carcinoma (CC) cell lines and tumor samples. 22 Loss of heterozygosity (LOH) is a common molecular genetic alteration found in human cancers, which may result in the loss of a normal tumor suppressor gene allele, thereby promoting cell growth and conferring survival advantages during tumorigenesis. Therefore, NOL7 is considered a tumor suppressor gene candidate.…”

“…2A). 22 In order to identify the nucleolar compartment in which NOL7-SP1 resides we performed co-localization experiments with known nucleolar markers. NOL7-SP1 exhibited a rounded nucleolar pattern reminiscent of GC proteins.…”