Related Experiment Video

Updated: Feb 25, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.3K

Regenerating Family Member 4 (Reg4) Enhances 5-Fluorouracil Resistance of Gastric Cancer Through Activating

Jiaoyue Jin1, Hang Lv2, Junzhou Wu1

  • 1Cancer Research Institute, Zhejiang Cancer Hospital and Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province, Hangzhou, Zhejiang, China (mainland).

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
|August 1, 2017
PubMed

Insights

Reg4 protein enhances gastric cancer resistance to 5-fluorouracil (5-FU) by inhibiting apoptosis. This occurs through the MAPK/Erk/Bim signaling pathway, not by affecting 5-FU metabolism.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Reg4, a Reg multigene family member, is upregulated in gastrointestinal cancers, including gastric cancer (GC).
  • Enhanced Reg4 expression correlates with 5-fluorouracil (5-FU) resistance in GC, but the mechanism remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which Reg4 confers resistance to 5-FU in gastric cancer.
  • To investigate the role of Reg4 in regulating apoptosis and cellular signaling pathways in response to 5-FU treatment.

Main Methods:

  • Assessed Reg4 expression in five GC cell lines using Western blot.
  • Manipulated Reg4 expression via plasmid transfection and siRNA knockdown in vitro.
  • Evaluated cell viability (MTT assay) and apoptosis (flow cytometry) following 5-FU treatment.
  • Examined 5-FU metabolic enzyme expression (RT-qPCR) and intracellular signaling pathways (Western blot).

Main Results:

  • Reg4 expression varied across GC cell lines, being high in AGS, MKN28, and MKN45, and low/null in SGC-7901 and BGC-823.
  • Reg4 overexpression increased cell viability and reduced 5-FU-induced apoptosis, while Reg4 knockdown enhanced apoptosis.
  • Reg4 did not significantly alter the expression of 5-FU metabolic enzymes.
  • Reg4 activation of the Erk1/2-Bim-caspase3 cascade was identified as a key mechanism.

Conclusions:

  • Reg4 confers 5-FU resistance in gastric cancer by inhibiting apoptosis.
  • The mechanism involves the regulation of the MAPK/Erk/Bim signaling pathway.
  • Reg4 represents a potential therapeutic target for overcoming 5-FU resistance in GC.

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.5K
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT10:28

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT

Published on: January 22, 2018

11.6K

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
51
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...
8.2K
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...
4.9K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
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...
8.8K
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...
5.3K