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.


METHODS
Total RNA was extracted from three pancreatic cancer cell lines (Panc-1, MIA 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.


CONCLUSIONS
Expression of SSTR-2 and SSTR-5 could be important in the growth inhibitory effect of somatostatin in human pancreatic cancer. Down-regulation of SSTR transcription or SSTR mRNA instability may result in loss of a tumor suppressive effect of SSTRs in human pancreatic cancer.
Li
Min
M
Elkins Pancreas Center and Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Li
Wei
W
Kim
Hee Joon
HJ
Yao
Qizhi
Q
Chen
Changyi
C
Fisher
William E
WE
D000230:Adenocarcinoma; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010190:Pancreatic Neoplasms; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C101130:somatostatin receptor type 1; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2