Disease relevance of AIM2

• Cytoplasmic localization of the interferon-inducible protein that is encoded by the AIM2 (absent in melanoma) gene from the 200-gene family [1].
• AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model [2].
• AIM-2: a novel tumor antigen is expressed and presented by human glioma cells [3].
• AIM-2 antigen is expressed in a wide variety of tumor types, including neuroectodermal tumors, as well as breast, ovarian and colon carcinomas [3].
• In this study, we analyzed AIM-2 expression in glioblastoma multiforme (GBM) in primary cultured cells and established GBM cell lines [3].

High impact information on AIM2

• In addition, we have localized AIM2 to the long arm of human chromosome 1 (band q22) in a highly conserved region which also contains the known interferon-inducible genes IFI16 and MNDA [4].
• We demonstrate that the AIM2 gene encodes a transcript of approximately 2 kb which is expressed in spleen, small intestine, and peripheral blood leukocytes [4].
• The AIM2 gene is a newly identified gene that is not expressed in a human melanoma cell line [1].
• Interestingly, overexpression of AIM2 in transfected cells retards proliferation and, under reduced serum conditions, increases the susceptibility to cell death [1].
• Although the AIM2 protein contained many of the conserved structural motifs common to other HIN-200 proteins, the biochemical characteristics of AIM2 and the ability of overexpressed AIM2 to phenocopy the effect of introduction of chromosome 6 in the UACC903 cells had not been assessed [5].

Biological context of AIM2

• The human HIN-200 family member AIM2 was originally identified in a screen for suppressors of melanoma tumorigenicity following introduction of chromosome 6 into the UACC903 human melanoma cell line [5].
• These data indicate that AIM2 has many of the biochemical and structural characteristics of HIN-200 proteins, however, its expression is not sufficient to induce a tumor-suppressor-like phenotype [5].
• Although AIM2 is known to inhibit fibroblast cell growth in vitro, its antitumor activity has not been shown [2].
• We further showed that AIM2 significantly increased sub-G(1) phase cell population, indicating that AIM2 could induce tumor cell apoptosis [2].
• The AIM-2 transcript seemed to have retained an intronic sequence based on its alignment with genomic sequences as well as expressed sequence tags [6].

Anatomical context of AIM2

• Antigen isolated from Immunoselected Melanoma-2 (AIM-2) was recently identified using melanoma-reactive CD8 T cells [3].
• More importantly, seven out of 12 HLA-A1 and AIM-2 positive patients from our dendritic cell clinical trial generated AIM-2 specific CTL activity in their PBMC after vaccinations [3].

Other interactions of AIM2

• The human IFN-inducible protein absent in melanoma 2 (AIM2) gene encodes a 39-kDa protein, which contains a 200-amino-acid repeat as a signature of HIN-200 family (hematopoietic IFN-inducible nuclear proteins) [2].

Analytical, diagnostic and therapeutic context of AIM2

• Together, these results suggest that AIM2 associates with tumor suppression activity and may serve as a potential therapeutic gene for future development of AIM2-based gene therapy for human breast cancer [2].
• These data indicate that AIM-2 could be used as a tumor antigen target for monitoring vaccine trials or to develop antigen specific active immunotherapy for glioma patients [3].
• AIM 2 used the 1997 Nationwide Inpatient Sample (NIS), with 895,259 pregnancy-related hospitalizations, to examine PAMC risks for groups likely to have prenatal care access problems [7].

References