Differential expression of GHRH receptor and its splice variant 1 in human normal and malignant mucosa of the oesophagus and colon.
Recent evidence indicates that growth hormone-releasing hormone (GHRH) functions as a growth factor for gastrointestinal (GI) tumours. The tumourigenic effects of GHRH appear to be mediated by the splice variant 1 (SV-1) of GHRH receptor as well as the full length pituitary type receptor for GHRH (GHRH-R). We examined the protein and mRNA expression of GHRH-R and SV-1 in normal human tissues and tumours of the gastrointestinal (GI-) tract by immunohistochemical staining and reverse transcriptase (RT)-PCR. Squamous cells and squamous cell carcinoma of the oesophagus were negative for GHRH-R and SV-1, while Barrett's mucosa and adenocarcinomas of the oesophagus showed a strong expression of both receptors. The expression of GHRH-R was absent in normal colonic mucosa other than neuroendocrine cells (NE) and lining epithelium (LE) but strong in tubular adenomas of the colon, while the staining for SV-1 was absent in cells other than NE. However, the expression of both receptors was significantly increased in tubulovillous adenomas and colorectal cancers. No differences were seen in protein levels for both receptors between normal and neoplastic tissues of the stomach, pancreas and liver. Because of low mRNA levels for both receptors in all samples tested, only a qualitative assessment could be made. However, mRNA for GHRH-R and SV-1 showed a near-perfect correlation with the assessment of receptor proteins by immunostaining. Our study shows that in contrast to normal mucosa, transformed mucosa of the oesophagus and the colon expresses GHRH-R and SV-1. This aberrant expression of GHRH-R and SV-1 in oesophageal and colorectal malignancies may provide a molecular target for a therapeutic approach based on GHRH antagonists.
Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, 5110 Oberndorf, Austria.
Florian
F
Hohla
Angelika
A
Moder
Ursula
U
Mayrhauser
Cornelia
C
Hauser-Kronberger
Andrew V
AV
Schally
Jozsef L
JL
Varga
Marta
M
Zarandi
Stefan
S
Buchholz
Rudolf
R
Huber
Elmar
E
Aigner
Markus
M
Ritter
Christian
C
Datz
D003106:Colon / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D019938:Cyclin D1 / Q000502:physiology; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D004947:Esophagus / Q000737:chemistry*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D018013:Receptors, Neuropeptide / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000032:analysis* / Q000737:chemistry / Q000235:genetics
D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D019938:Cyclin D1; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor