Heat shock protein 70 (Hsp70) subtype expression in neuroendocrine tissue and identification of a neuroendocrine tumour-specific Hsp70 truncation

Autor: Ludwig Wagner, M Weissel, Bruno Niederle, Barbara Zierhut, W Gartner, W Base, T. Daneva, Karl Mechtler
Rok vydání: 2004
Předmět:
Zdroj: Endocrine-related cancer. 11:377-389
ISSN: 1351-0088
DOI: 10.1677/erc.0.0110377
Popis: In order to identify neuroendocrine tumour-specific protein expression, we generated monoclonal antibodies (mAbs) with a tumour-related reaction pattern using a human insulinoma as immunogen. One of the generated mAbs (mAb 1D4) exhibited striking immunoreactivity against various neuroendocrine tumours without staining pancreatic islets of Langerhans. Furthermore, mAb 1D4 immunostained a characteristic subtype of hypothalamic neurones. Using two-dimensional (2-D) gel electrophoresis, mAb 1D4 immunoblotting and mass spectrometry, heat shock protein 70 (Hsp70) isoforms were identified as the mAb 1D4-specific antigen. In hypothalamic tissue, the presence of two different Hsp70 isoforms (Hsp70-8 and Hsp70-1) was revealed by 2-D gel immunoblots and consecutive mass spectrometric peptide analysis. In contrast, insulinoma and other neuroendocrine tumours displayed solely Hsp70-8 expression. Moreover, the tumour-specific presence of an additional mAb 1D4 immunoreactive protein of 40 kDa was observed in eight out of eight tested neuroendocrine tumours. For this variant, exclusively, peptides derived from the C terminus excluding the 299 amino-terminal residues were detected. In cultured tumour-derived fibroblasts, expression of the truncated Hsp70-8 subtype was not present. In conclusion, we have demonstrated a neuroendocrine tumour-specific expression pattern of Hsp70 isoforms and identified an as yet unknown N-terminally truncated Hsp70-8 variant. Endocrine-Related Cancer (2004) 11 377–389
Databáze: OpenAIRE