Anti-MIA2 monoclonal antibody, clone 3C0

Melanoma inhibitory activity (MIA) gene family members include MIA, MIA2, and Transport and Golgi organization protein 1 (TANGO). Although MIA gene family members have several tumor-related functions, their detailed roles in malignancies remain poorly elucidated. In this study, 477 tumor specimens were subjected to immunohistochemical screening to evaluate MIA gene family expression. For a validation analysis, we also examined the association between MIA gene family expression and clinicopathological factors in 66 cases of esophageal cancer, 145 cases of lung cancer, and 126 cases of cervical cancer. The frequency of MIA gene family expression was higher among squamous cell carcinomas than among other tumor types subjected to screening. In the validation analysis, MIA gene family staining was observed frequently in esophageal and lung cancers associated with nodal and/or distant metastasis. In cervical cancers, MIA and TANGO immunostaining also correlated with tumor progression and metastasis. Furthermore, MIA2 expression levels in invasive cervical cancer were upregulated relative to those in cervical intraepithelial neoplasia 3. A disease-free survival analysis revealed that MIA-, MIA2, or TANGO-positive patients had a significantly shorter disease-free survival than did those patients who were negative. Our results suggest that MIA, MIA2, and TANGO may be useful diagnostic and therapeutic molecular targets in human malignancies.

A novel human gene, TANGO, encoding a MIA ('melanoma inhibitory activity') homologous protein was identified by a gene bank search. TANGO, together with the homologous genes MIA, OTOR (FPD, MIAL) and MIA2 define a novel gene family sharing important structural features, significant homology at both the nucleotide and protein level, and similar genomic organization. The four members share 34-45% amino acid identity and 47-59% cDNA sequence identity. TANGO encodes a mature protein of 103 amino acids in addition to a hydrophobic secretory signal sequence. Sequence homology confirms the highly conserved SH3 structure present also in MIA, OTOR and MIA2. Thus, it appears that there are a number of extracellular proteins with SH3-fold like structures. Interestingly, in situ hybridization, RTPCR and Northern Blots revealed very broad TANGO expression patterns in contrast to the highly restricted expression patterns previously determined for the other members of the MIA gene family. The only cells lacking TANGO expression are cells belonging to the hematopoetic system. High levels of TANGO expression were observed both during embryogenesis and in adult tissues. (C) 2003 Elsevier B.V. All rights reserved.