Characterization of somatostatin receptor expression in human pancreatic cancer using real-time RT-PCR

Background. Somatostatin inhibits cell proliferation and may act as a tumor suppressor by interacting with five different somatostatin receptors (SSTRs). We hypothesized that SSTR expression is down-regulated in human pancreatic cancer. In the current study, we used a powerful real-time RT-PCR technique to examine the mRNA expression levels of all five SSTR subtypes in human pancreatic cancer. Materials and methods. Total RNA was extracted from three pancreatic cancer cell lines (Panc-1, NHA PaCa-2, and Hs 766T), three surgical specimens of pancreatic cancer, and adjacent pancreatic tissue, and a pancreatic cancer cell line transfected with the SSTR-2 gene. Specific primers were designed and mRNA levels for the five SSTRs were analyzed with real-time quantitative RT-PCR using a Bio-Rad iCycler system. Results. The pancreatic tumor specimens had a 2.5 and 4.3-fold reduction of SSTR-2 and SSTR-5 mRNA levels, respectively, as compared to their adjacent normal pancreatic tissues. SSTR-1 and SSTR-3 were also detected in both the cancer specimens and the adjacent tissues, but SSTR-4 was absent. Human pancreatic cancer cell lines also expressed SSTR-2 and SSTR-5 mRNA, but not SSTR-1, SSTR-3, and SSTR-4. Up-regulation of SSTR-2 mRNA by 2.2 X 10(4) -fold in Panc-1 cells resulted in receptor expression and growth inhibition. Conclusion. Expression of SSTR-2 and SSTR-5 could be important in the growth inhibitory effect of somatostatin in human pancreatic cancer. Downregulation of SSTR transcription or SSTR mRNA instability may result in loss of a tumor suppressive effect of SSTRs in human pancreatic cancer. (C) 2004 Elsevier Inc. All rights reserved.