Related Experiment Video

Updated: Oct 8, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
09:40

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation

Published on: June 27, 2017

Transcriptional activation of mouse sst2 somatostatin receptor promoter by transforming growth factor-beta.

E Puente1, N Saint-Laurent, J Torrisani

  • 1INSERM U 531, Institut Louis Bugnard, 31403, Toulouse, France.

The Journal of Biological Chemistry
|March 30, 2001
PubMed

Insights

The somatostatin receptor 2 (sst2) gene, crucial for inhibiting tumor growth, is often lost in pancreatic cancers. This study identifies key regulatory elements and shows that TGF-beta, via Smad4, can restore sst2 expression, offering potential therapeutic insights.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The somatostatin receptor 2 (sst2) is an inhibitory G protein-coupled receptor with anti-tumor properties.
  • sst2 expression is frequently lost in human pancreatic cancers, suggesting a role in tumor progression.

Purpose of the Study:

  • To identify regulatory elements controlling mouse sst2 (msst2) gene transcription.
  • To investigate the role of transforming growth factor-beta (TGF-beta) and Smad proteins in msst2 regulation.
  • To explore the potential link between Smad4 deficiency, sst2 loss, and pancreatic cancer growth.

Main Methods:

  • Cloning of the upstream genomic DNA region of msst2.
  • Deletion reporter analyses in various cell lines (AtT-20, PANC-1, BxPC-3, Capan-1).
  • Investigating TGF-beta-mediated transactivation using Smad3 and Smad4, and analyzing cis-acting elements (Sp1, CAGA-box).

Main Results:

  • A 325-base pair region (-260 to ATG) showed maximal promoter activity; a silencer region was identified between -2025 and -260.
  • TGF-beta up-regulates msst2 transcription in PANC-1 and AtT-20 cells, mediated by Smad4 and Smad3.
  • Expression of Smad4 restored TGF-beta-dependent/independent msst2 transactivation in deficient cells and reestablished sst2 expression and somatostatin-mediated growth inhibition in BxPC-3 cells.

Conclusions:

  • msst2 is a novel target gene for TGF-beta transcriptional regulation.
  • Loss of Smad4 may contribute to the lack of sst2 expression in pancreatic cancer, potentially promoting tumor growth.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System11:06

Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System

Published on: July 30, 2018

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...