In addition to inhibiting pituitary GH secretion, somatostatin (SS) and its analogues have been shown to exert anti-proliferative effects on a variety of different cell types. The presence of receptors for SS have been demonstrated in a number of tissues but quantification of mRNA expression of the 5 subtypes of SSTR in the colon is unknown.
Total RNA was extracted from 9 paired samples of adjacent normal (AN) and malignant (T) colon obtained at surgery, from 9 biopsies of normal colon (NN) obtained at colonoscopy from patients without colonic pathology, and from HT29 cells, a human colorectal cancer cell line. Informed consent was obtained from all patients. mRNA levels for SS and SSTR subtypes 1-5 were quantified using real-time RT-PCR (Taqman) and expressed as copy number/ ug total RNA.
SS was expressed by all NN patients (median copy no 4.20E+06) but in only 6/9 AN (1.40E+05, p=<0.05) and only 3/9 T patients (2.00E+00, p<0.05).
All patients expressed SSTR-1 - median of 9.69E+07 (NN), 3.69E+07 (AN), 2.11E+07 (T) respectively. There was no difference in the universal expression level of SSTR-3 and SSTR-5 between NN, AN and T samples but SSTR-2 and SSTR-4 mRNA levels were higher in NN (5.90E+07 and 4.22E+07 respectively) than AN (4.91E+07 and 1.83E+07 respectively) and significantly higher than T (1.76E+07 and 8.65E+06 respectively p<0.05).
The increased expression of SS in normal colon suggests a local role for this peptide in tissue homeostasis. The universal expression of all the SSTR subtypes in colon cancer offers potential chemotherapeutic benefit with broad-acting SS analogues such as SOM 230.
22 - 24 Mar 2004
British Endocrine Societies