SOMATOSTATIN RECEPTOR SUBTYPE MESSENGER-RNA EXPRESSION IN HUMAN COLORECTAL-CANCER AND NORMAL COLONIC MUCOSAE

Somatostatin analogues may be useful novel agents in the systemic trea tment of advanced colorectal cancer, as somatostatin inhibits prolifer ation in a wide variety of cell types. Here, we report the expression profiles of somatostatin receptor mRNAs in 32 pairs of malignant and n ormal colonic epithelia. Receptor subtype 2 (hSSTR2) mRNA was detected throughout nearly 90% of both malignant and normal tissue by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridiza tion. Subtype 5 (hSSTR5) mRNA was detected in 46% and 45% of tumour an d mucosal samples respectively, but in 75% (9/12) of early-stage tumou rs (tubulovillous adenomas, Dukes' A and B) compared with 31% (5/16) o f late-stage tumours (Dukes' C and 'D' tumours), 0.05>P>0.025 (chi(2) with Yates' correction). There was also reduced expression of hSSTR5 i n samples of metastatic tumour (11%, 1/9) compared with all tumour sam ples (56%, 18/32) 0.025>P>0.01 (chi(2) with Yates' correction). Other hSSTRs (1, 3 and 4) were expressed infrequently. Thus, hSSTR2 expressi on is retained after malignant transformation in colonic epithelium an d, although it may potentially be a target for antiproliferative thera py, its ubiquitous expression militates against this. hSSTR5 warrants investigation as a tumour suppressor.