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Updated: Sep 30, 2026
Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles
Published on: January 4, 2012
Somatostatin receptor subtype 2 gene therapy inhibits pancreatic cancer in vitro
William E Fisher1, YuanQing Wu, Felipe Amaya
1Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. wfisher@bcm.tmc.edu
Background:
Most human pancreatic adenocarcinoma cells do not express somatostatin receptors and somatostatin does not inhibit the growth of these cancers. We have demonstrated previously that somatostatin inhibits the growth of pancreatic cancers expressing somatostatin receptor subtype 2 (SSR2) but not receptor-negative cancers. SSR2 expression may be an important tumor suppressor pathway that is lost in human pancreatic cancer. We hypothesized that SSR2 gene transfer would restore the growth inhibitory response of human pancreatic cancer to somatostatin.
Methods:
We created adenoviral constructs containing the SSR2 or Lac-Z gene and transfected somatostatin receptor-negative human pancreatic cancer cells (Panc-1). Presence of functional cell surface SSR2 protein was assessed by whole-cell competitive binding assays. Parental cells, Lac-Z-transfected, and SSR2-transfected cells were cultured in the presence and absence of somatostatin. The rate of cell growth was determined by direct cell counting using a hemacytometer (n = 8 wells/group). Cells were analyzed for expression of tumor suppressor proteins by Western blot.
Results:
Panc-1 cells transfected with the SSR2 transgene demonstrated high-affinity specific binding of (125)I-somatostatin at physiologic concentrations. Expression of somatostatin receptors caused 60% inhibition of cell growth compared with the Lac-Z virus-treated controls (P < 0.05 by Kruskal-Wallis/Bonferroni). There was no additional inhibition of cell proliferation with exogenous somatostatin. Furthermore, addition of somatostatin ligand antibody did not diminish the effect of SSR2 expression on cell proliferation. Western blot analysis revealed an upregulation of the cyclin-dependent kinase inhibitor p27 in the SSR2-transfected cells.
Conclusions:
Expression of SSR2 by human pancreatic cancer causes significant slowing of cell division by a mechanism independent of somatostatin. The mechanism may involve upregulation of known tumor suppressor proteins. Restoration of SSR2 gene expression deserves further study as a potential gene therapy strategy in human pancreatic cancer.
Insights
Restoring somatostatin receptor subtype 2 (SSR2) in pancreatic cancer cells significantly slowed their growth. This SSR2 gene expression inhibits cancer cell division independently of somatostatin, suggesting a potential gene therapy approach.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Most pancreatic adenocarcinomas lack somatostatin receptors, rendering them unresponsive to somatostatin's growth-inhibitory effects.
- Previous research indicates somatostatin inhibits pancreatic cancer growth only in tumors expressing somatostatin receptor subtype 2 (SSR2).
- SSR2 expression may function as a tumor suppressor pathway frequently lost in pancreatic cancers.
Purpose of the Study:
- To investigate if transferring the SSR2 gene into pancreatic cancer cells can restore their sensitivity to somatostatin.
- To determine the effect of SSR2 gene transfer on the growth of somatostatin receptor-negative pancreatic cancer cells.
Main Methods:
- Adenoviral vectors carrying SSR2 or Lac-Z genes were used to transfect Panc-1 human pancreatic cancer cells.
- Functional cell surface SSR2 expression was confirmed using competitive binding assays.
- Cell growth rates were measured, and tumor suppressor protein expression was analyzed via Western blot.
Main Results:
- SSR2-transfected Panc-1 cells exhibited specific binding of somatostatin.
- SSR2 expression led to a 60% inhibition of cell growth compared to controls (p < 0.05).
- Upregulation of the tumor suppressor protein p27 was observed in SSR2-transfected cells.
Conclusions:
- SSR2 expression in pancreatic cancer cells significantly inhibits cell division through a somatostatin-independent mechanism.
- This mechanism may involve the upregulation of tumor suppressor proteins like p27.
- Restoring SSR2 gene expression shows promise as a potential gene therapy strategy for pancreatic cancer.
