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
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.