Related Experiment Video

Updated: Aug 16, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

A transforming growth factor-beta receptor-interacting protein frequently mutated in human ovarian cancer

Wei Ding1, Qian Tang, Virginia Espina

  • 1Department of Pharmacology and Health Evaluation Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.

Cancer Research
|August 3, 2005
PubMed

Insights

Transforming growth factor-beta (TGF-beta) resistance in ovarian cancer is linked to alterations in the km23 protein. These changes disrupt dynein motor complex formation and TGF-beta signaling, impacting tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian carcinomas often exhibit resistance to transforming growth factor-beta (TGF-beta)-mediated growth inhibition.
  • Mutations in TGF-beta receptor genes are infrequent, suggesting other TGF-beta pathway components are involved in resistance.

Purpose of the Study:

  • To investigate alterations in the km23 gene, which interacts with the TGF-beta receptor complex, in ovarian cancer.
  • To determine the role of km23 alterations in TGF-beta resistance and tumor progression.

Main Methods:

  • Laser-capture microdissection and nested reverse-transcription-PCR were used to analyze km23 in tumor tissues.
  • Functional studies assessed the impact of km23 mutations on dynein binding and TGF-beta signaling.

Main Results:

  • High frequency of km23 alterations (42.1%) found in ovarian cancer tissues, including exon deletions and missense mutations.
  • Mutant km23 forms (Deltaexon3-km23, S55G/I89V-km23) showed disrupted binding to dynein intermediate chain.
  • Deltaexon3-km23 inhibited TGF-beta-dependent transcriptional activation.

Conclusions:

  • Alterations in km23 are common in ovarian cancer and may contribute to TGF-beta resistance.
  • These alterations can lead to defects in dynein motor complex formation and aberrant TGF-beta transcriptional regulation.

More Related Videos

Transplantation Into the Mouse Ovarian Fat Pad09:25

Transplantation Into the Mouse Ovarian Fat Pad

Published on: September 7, 2016

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

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...
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...
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...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
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...