Related Experiment Video

Updated: May 7, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

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

19.0K

AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines

Pamela Leal1, Patricia Garcia, Alejandra Sandoval

  • 1Department of Pathology, Universidad de La Frontera, Center of Genetical and Immunological Studies-Scientific and Technological Bioresource Nucleus, Temuco, Santiago, Chile.

Oncotargets and Therapy
|October 15, 2013
PubMed
Abstract

Insights

The mammalian target of the rapamycin (mTOR) pathway is upregulated in gallbladder carcinoma. mTOR inhibitors show promise in reducing gallbladder cancer cell growth and migration, suggesting a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Gallbladder carcinoma is a highly aggressive cancer with poor prognosis and resistance to conventional therapies.
  • The mammalian target of rapamycin (mTOR) signaling pathway is implicated in various human malignancies.
  • There is a critical need for novel therapeutic strategies for gallbladder carcinoma.

Purpose of the Study:

  • To investigate the role of the mTOR pathway in gallbladder carcinoma by examining the phosphorylation status of its substrate p70S6K.
  • To evaluate the efficacy of three mTOR inhibitors (rapamycin, RAD001, AZD8055) in preclinical gallbladder carcinoma models.

Main Methods:

  • Immunohistochemical analysis of phospho-p70S6K in 181 gallbladder carcinoma tissues (dysplasia, early, and advanced stages).
  • Western blot analysis of AKT/mTOR pathway members in eight gallbladder carcinoma cell lines.
  • In vitro assessment of mTOR inhibitors' effects on cell viability and migration in two selected gallbladder carcinoma cell lines (G415 and TGBC-2TKB).

Main Results:

  • Phospho-p70S6K was highly expressed across all stages of gallbladder lesions, including dysplasia, early, and advanced carcinoma.
  • No significant correlation was found between phospho-p70S6K expression and clinical or pathological features.
  • Treatment with rapamycin, RAD001, and AZD8055 significantly inhibited cell growth, migration, and reduced phospho-p70S6K expression in gallbladder cancer cell lines.

Conclusions:

  • The findings confirm the upregulation of the mTOR signaling pathway in gallbladder carcinoma.
  • mTOR inhibitors demonstrate significant anti-cancer effects in vitro, supporting their potential as a therapeutic approach.
  • Targeting the mTOR pathway represents a promising strategy for future gallbladder carcinoma treatment.
Keywords:
AKTcell linegallbladder cancermTOR inhibitormigrationp70S6K

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.3K
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

5.7K

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...
3.6K
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...
5.2K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
12.2K
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...
4.0K
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
44.8K