DNA Methyltransferase Inhibitor Hydralazine Induces Upregulation of Somatostatin Type 2 Receptors in Human Neuroendocrine Tumor Cells Abstract #2905

Introduction: Epidrugs like DNA methyltransferase inhibitors (DNMTi) can increase somatostatin receptor type 2 (SST2) expression in neuroendocrine tumor (NET) cells in vitro and in vivo. This effect could be used for NET patients with low SST2 expression who are currently ineligible for somatostatin analogue (SSA) treatment. However, the DNMTi known to stimulate SST2 have either a high toxicity profile or are not yet approved.
Aim(s): Evaluation of the antihypertensive and DNMTi drug hydralazine as epidrug for SST2 upregulation.
Materials and methods: Human NET cell lines BON-1 (pancreatic) and GOT-1 (small intestine) were treated with hydralazine alone and in combination with the histone deacetylase inhibitor (HDACi) valproic acid. SST2 expression was determined by RT-qPCR and internalization studies with radiolabelled somatostatin analogue were performed.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Genetics, epigenetics, miRNAs, Omics
Presenting Author: Dr Julie Refardt

To read results and conclusion, please login ...

Further abstracts you may be interested in

#62 Genome-wide DNA methylation profiling of pancreatic neuroendocrine tumors identifies distinct methylation profiles and differentially methylated gene promoter regions associated with low, medium and high grade tumors
Introduction: Integration of genetics and epigenetics has emerged as a powerful approach to studying cellular differentiation (Mikkelsen et al, 2009) and tumorigenesis (Shen et al, 2007). The study of DNA methylation is of particular importance in cancer, as causal involvement has been demonstrated and it is the most stable of all epigenetic modifications, making it a desirable marker for both early detection and treatment of tumors. Hypermethylation of CpG sites in gene promoter regions leads to decreased gene expression; if such a gene is a tumor suppressor, this leads to carcinogenesis. To date, there have been no studies of genome-wide DNA methylation profiling of NETs. This study sets out to determine the DNA methylation profiles of low, intermediate and high grade pancreatic NET liver metastases with the intention of identifying dysregulated biological pathways in the development of these tumors. A protocol for the analysis formalin-fixed paraffin embedded tissue (FFPE) has also been developed in order to study these tumors in significant numbers following this pilot study.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr Christina Thirlwell
#245 Expression of Somatostatin Receptors and Dopamine 2 Receptor in Lung Carcinoids as a Possible Biotherapy Target
Introduction: Expression of somatostatin receptors (SSTRs) and dopamine 2 receptor (D2R) in neuroendocrine tumors is of clinical importance, as somatostatin analogues and dopamine agonists are used in biotherapy.
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: Dr Apostolos V. Tsolakis
#302 Monoclonal Antibodies Against the Human Somatostatin Receptor Subtypes 1-5: Characterization and Immunohistochemical Application in Gastrointestinal Neuroendocrine Tumors
Introduction: A lack of well-characterized somatostatin receptor (sstr)-specific antibodies has hampered development of routine sstr expression profiles that may be useful in the treatment of NET patients (pts).
Conference: 8th Annual ENETS Conference (2011)
Category: Clinical
Presenting Author: Chiara Lambertini
#976 Upregulation of Somatostatin Receptor Type 2 Expression in Neuroendocrine Tumors by Epigenetic Modulation
Introduction: The somatostatin receptor type 2 (sst2) is a target for treatment of neuroendocrine tumors (NETs). However, epigenetic mechanisms might account for the high variability in sst2 expression and treatment response between patients.
Conference: 11th Annual ENETS Conference 2014 (2014)
Category: Basic Science - Genetics, epigenetics, miRNAs
Presenting Author: MSc Marije J Veenstra
Keywords: GEP-NET, sst2, epigenetics
#1097 Epigenetic Manipulation of the Somatostatin Receptor Type 2 in Neuroendocrine Tumor Cells
Introduction: The somatostatin receptor type 2 (sst2) is a target for treatment in patients with neuroendocrine tumors (NET). However, variability in tumoral sst2 expression might lead to variability in response. Epidrugs could increase sst2 levels and improve response to somatostatin analogues (SSA).
Conference: 12th Annual ENETS Conference 2015 (2015)
Category: Basic Science - Genetics, epigenetics, miRNAs
Presenting Author: Marije Jildau Veenstra
Keywords: NET, sst2, epidrug, signaling