Down-regulation of nerve growth factor in poorly differentiated and advanced human esophageal cancer.
BACKGROUND
Binding of nerve growth factor (NGF) to its receptor TrkA leads to intracellular tyrosine kinase activation and regulates the growth and differentiation of various non-neuronal tumours.


METHODS
In the present study NGF and TrkA were analysed by Northern blot analysis, in situ hybridisation and immunohistochemistry in 41 esophageal cancer samples in comparison to normal controls.


RESULTS
NGF mRNA (P < 0.01), but not TrkA mRNA was down-regulated in esophageal cancer samples compared with normal tissues. In the normal esophagus, NGF mRNA and protein was present in epithelial cells of the entire epithelial layer and TrkA mRNA and protein was present in epithelial cells of the basal layer. In esophageal cancer NGF and TrkA mRNA and protein were present in the cancer cells. Down-regulation of NGF correlated with poor differentiation (P < 0.01) and advanced tumour stage (P < 0.01). Low TrkA expression was related to advanced tumour stage (P < 0.05).


CONCLUSIONS
A loss of activation of the NGF/TrkA pathway occurs during tumour progression and may contribute to loss of tumour differentiation in esophageal cancer.
Zhu
Z W
ZW
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Friess
H
H
Wang
L
L
Di Mola
F F
FF
Zimmermann
A
A
Büchler
M W
MW
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D004947:Esophagus / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020917:Receptor, trkA / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020932:Nerve Growth Factor; D020917:Receptor, trkA