Related Experiment Video

Updated: Aug 30, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

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

Published on: October 27, 2020

Tuberous sclerosis-2 tumor suppressor modulates ERK and B-Raf activity in transformed renal epithelial cells

Hae-Seong Yoon1, Sampath Ramachandiran, Mary Anne S Chacko

  • 1Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Texas 78712, USA.

American Journal of Physiology. Renal Physiology
|November 13, 2003
PubMed

Insights

The tuberous sclerosis-2 (Tsc-2) gene, or tuberin, suppresses kidney tumors by negatively regulating the ERK pathway. Loss of tuberin function leads to increased cell proliferation and tumor formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The tuberous sclerosis-2 (Tsc-2) gene and its protein product, tuberin, are known suppressors of renal tumorigenesis.
  • The precise mechanism by which tuberin regulates cell proliferation and suppresses tumor formation remains largely unknown.
  • Loss of tuberin expression is associated with increased ERK pathway activity, a key factor in renal cancer development.

Purpose of the Study:

  • To investigate the mechanism by which tuberin exerts its antiproliferative action.
  • To identify downstream effectors regulated by tuberin in renal epithelial cells.
  • To elucidate the role of tuberin in regulating the ERK signaling pathway in the context of renal cancer.

Main Methods:

  • Utilized quinol-thioether-transformed rat renal epithelial (QT-RRE) cell lines lacking tuberin expression.
  • Restored tuberin expression in QT-RRE cells via transient transfection with Tsc-2 cDNA.
  • Assessed the activity of ERK, B-Raf, and Raf-1 signaling pathways before and after tuberin restoration.
  • Investigated the involvement of EGF receptor and protein kinases in the ERK cascade.

Main Results:

  • QT-RRE cells exhibited constitutively high ERK, B-Raf, and Raf-1 activities.
  • Restoration of tuberin expression significantly decreased ERK and B-Raf activity, indicating tuberin's role as an upstream negative regulator.
  • High ERK activity was not mediated by EGF receptor but involved protein kinases.
  • Loss of tuberin function correlated with increased DNA synthesis and potential for tumor formation.

Conclusions:

  • Tuberin functions as an upstream negative regulator of the ERK signaling pathway.
  • Loss of tuberin leads to the upregulation of the ERK pathway, promoting cell proliferation and contributing to renal tumor formation.
  • Understanding tuberin's role in ERK regulation offers insights into therapeutic strategies for Tsc-2-associated renal cancers.

More Related Videos

Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...