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Transfection of SSTR-1 and SSTR-2 Inhibits Panc-1 Cell Proliferation and Renders Panc-1 Cells Responsive to Somatostatin Analogue
- Source :
-
Journal of the American College of Surgeons . Oct2005, Vol. 201 Issue 4, p571-578. 8p. - Publication Year :
- 2005
-
Abstract
- <bold>Background: </bold>Somatostatin inhibits cell proliferation through interaction with its cellular receptor, somatostatin receptors (SSTRs). We have previously demonstrated that overexpression of individual SSTR-1 or SSTR-2 genes in receptor-negative pancreatic cancer cells inhibited cell proliferation. We hypothesize that reintroduction of SSTR genes back into pancreatic cancer cells might be an effective gene therapy strategy for pancreatic cancer.<bold>Study Design: </bold>We transfected human pancreatic cancer cell line (Panc-1) with human SSTR-1 and SSTR-2 genes and examined the expression by real-time reverse transcriptase-polymerase chain reaction and immunofluorescence. Panc-1 cell proliferation was determined by [(3)H]-thymidine incorporation assay. Activation of phosphorylated c-Jun N-terminal protein kinase (JNK) and cytokine secretion after SSTR-1 and SSTR-2 transfection were detected by Bio-Plex 4-plex phosphoprotein assay and cytokine assay.<bold>Results: </bold>Panc-1 cells did not express SSTR-1 or SSTR-2, although Panc-1 cells transfected with SSTR-1 and SSTR-2 genes showed a significant amount of SSTR expression. Cell growth rate in Panc-1 cells transfected with SSTR-1 and SSTR-2 was inhibited about 41%, and the cell proliferation of Panc-1 expressing SSTR-1 and SSTR-2 was further reduced about 12% on treatment with somatostatin analogue as compared with the control group. SSTR-1 and SSTR-2 cotransfected Panc-1 cells activated phosphorylation of JNK and increased secretion of interferon-gamma and interleukin-5.<bold>Conclusions: </bold>These findings suggest, for the first time, a synergistic inhibitory effect of multiple SSTRs in response to a somatostatin analogue in Panc-1 cells. These studies may improve our understanding of the mechanism by which SSTR inhibits cell growth and lead to novel gene therapies for pancreatic cancer. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CANCER treatment
*CANCER genetics
*ISLANDS of Langerhans
*CELL growth
*RNA analysis
*BIOCHEMISTRY
*CELL physiology
*CELL receptors
*COMPARATIVE studies
*DNA probes
*GENE therapy
*GENETIC techniques
*PHENOMENOLOGY
*RESEARCH methodology
*MEDICAL cooperation
*PANCREATIC tumors
*POLYMERASE chain reaction
*RESEARCH
*SOMATOSTATIN
*TRANSFERASES
*EVALUATION research
*REVERSE transcriptase polymerase chain reaction
*CANCER cell culture
Subjects
Details
- Language :
- English
- ISSN :
- 10727515
- Volume :
- 201
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of the American College of Surgeons
- Publication Type :
- Academic Journal
- Accession number :
- 18344533
- Full Text :
- https://doi.org/10.1016/j.jamcollsurg.2005.06.089