Related Experiment Video

Updated: Jul 4, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice

T Hasegawa1, A Enomoto, T Kato

  • 1Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Oncogene
|June 11, 2008
PubMed

Insights

Mitogen-activated protein kinase phosphatase-2 (MKP-2) is upregulated in RET-driven cancers, including medullary thyroid carcinoma. Inhibiting MKP-2 suppressed tumor cell proliferation by reducing cyclin B1 expression, highlighting MKP-2 as a key player in RET-mediated oncogenesis.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Germline mutations in the RET tyrosine kinase gene cause Multiple Endocrine Neoplasia (MEN2A and MEN2B).
  • The precise signaling mechanisms driven by mutant RET remain incompletely understood.

Purpose of the Study:

  • To investigate the role of mitogen-activated protein kinase phosphatase-2 (MKP-2) in RET-mediated oncogenesis.
  • To determine if MKP-2 is involved in the development of MEN2-associated carcinomas.

Main Methods:

  • Analysis of MKP-2 expression in transgenic mouse models with RET-MEN2A mutations and human MEN2A medullary thyroid carcinomas.
  • Investigating MKP-2 induction by mutant RET proteins and glial cell line-derived neurotrophic factor (GDNF).
  • Assessing the impact of MKP-2 inhibition on MKK-f cell proliferation and cyclin B1 expression in vitro and in vivo.

Main Results:

  • Increased MKP-2 expression was observed in RET-MEN2A transgenic mouse carcinomas and human MEN2A medullary thyroid carcinomas.
  • MKP-2 expression was induced by both mutant RET proteins (RET-MEN2A, RET-MEN2B) and activated endogenous RET.
  • Inhibition of MKP-2 reduced MKK-f cell proliferation and cyclin B1 expression, impacting cell cycle regulation.

Conclusions:

  • Elevated MKP-2 expression is a significant downstream event in mutant RET signaling.
  • MKP-2 plays a critical role in the proliferation of RET-driven cancers.
  • MKP-2 represents a potential therapeutic target for MEN2-associated malignancies.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

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...
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...
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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...