THE EWING TUMOR FAMILY OF PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMORSEXPRESSES HUMAN GASTRIN-RELEASING PEPTIDE

Citation
Er. Lawlor et al., THE EWING TUMOR FAMILY OF PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMORSEXPRESSES HUMAN GASTRIN-RELEASING PEPTIDE, Cancer research, 58(11), 1998, pp. 2469-2476
Citations number
54
Categorie Soggetti
Oncology
Journal title
ISSN journal
00085472
Volume
58
Issue
11
Year of publication
1998
Pages
2469 - 2476
Database
ISI
SICI code
0008-5472(1998)58:11<2469:TETFOP>2.0.ZU;2-Z
Abstract
The Ewing tumor family of peripheral primitive neuroectodermal tumors (pPNETs) are characterized by chromosomal translocations leading to EW S-ETS gene fusions, These hybrid genes express chimeric proteins that are thought to act as aberrant transcription factors. We therefore use d differential display-PCR to compare gene expression patterns in pPNE T cell lines with those of other small round cell tumors (SRCTs) of ch ildhood. This technique detected differential expression of sequences corresponding to human gastrin-releasing peptide (GRP) in pPNET cell l ines but not in other SRCT cell lines. Subsequent Northern and reverse transcription-PCR analysis of SRCT cell lines confirmed GRP positivit y in all pPNET lines tested. Of primary tumors tested by reverse trans cription-PCR, GRP expression was found in 7 (44%) of 16 pPNETs but in no other primary SRCTs examined. Expression of the GRP receptor gene a ,as demonstrable in 55% of pPNET cell lines and 25% of primary pPNET t umors but also in several other SRCTs, Radioimmunoassays and immunohis tochemistry confirmed expression of bioactive GRP peptide in pPNET cel l lines and primary tumors, respectively. Moreover, in vitro growth of a pPNET cell line was slowed by treatment with a GRP receptor antagon ist and accelerated by a GRP receptor agonist. GRP is a known autocrin e growth factor in small cell lung cancer and other neuroendocrine tum ors. Its expression in pPNETs provides further evidence for a neuroect odermal histogenesis of these tumors and suggests that autocrine growt h of this family of tumors may be at least partially regulated by GRP.