title: High gastrin releasing peptide receptor mRNA level is related to tumour dedifferentiation and lymphatic vessel invasion in human colon cancer.
abstract: The neuropeptide bombesin stimulates tumour cell proliferation in vitro. Through pharmacological testing, 20-40% of human colorectal tumours have been shown to be equipped with bombesin/gastrin releasing peptide receptor (GRP-R). The aim of the present study was to test whether GRP-R expression is correlated with tumour characteristics and usual prognostic factors in colorectal adenocarcinomas. A sensitive reverse transcription (RT)-competitive polymerase chain reaction (PCR) method was validated by studying GRP-R mRNA in separated layers of normal colonic wall, and GRP-R mRNA levels (in parallel with binding studies) in colon cancer cell lines LoVo and Caco-2. GRP-R mRNA levels were then determined in 29 surgical tumour specimens and the results compared with tumour histology and, using histochemistry, with the accumulation of p53 protein and a Ki-67 cell proliferation index. The mRNA was not detected in normal colonic epithelium, whereas a distinct signal was observed after amplification in 27/29 (93%) tumour specimens. Estimates of mRNA levels in the 27 positive tumours ranged from 52 to 8000 amol/0.25 microgram total RNA, and were significantly higher in poorly/moderately differentiated tumours (P < 0.05) and in tumours with lymphatic vessel invasion (P < 0.01). There was no relationship with p53 accumulation or to the proliferation index. Our results show that GRP-R mRNA can be detected in most colorectal tumour specimens, and suggest a link between high mRNA levels and both tumour dedifferentiation and lymph vessel invasion, but not proliferation.
authors.affiliation: Inserm U45, Hôpital Edouard-Herriot, Pavillon H, Lyon, France. saurin@lyon151.inserm.fr
authors.forename: J C
authors.initials: JC
authors.lastname: Saurin
authors.forename: J P
authors.initials: JP
authors.lastname: Rouault
authors.forename: J
authors.initials: J
authors.lastname: Abello
authors.forename: F
authors.initials: F
authors.lastname: Berger
authors.forename: L
authors.initials: L
authors.lastname: Remy
authors.forename: J A
authors.initials: JA
authors.lastname: Chayvialle
mesh_terms: D000368:Aged; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008206:Lymphatic Diseases / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019886:Gastrin-Releasing Peptide