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Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Hypoxia01:23

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Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
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Related Experiment Video

Updated: Sep 10, 2025

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
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Gene Expression in Muscle-Invasive and Non-Muscle-Invasive Bladder Cancer Cells Exposed to Hypoxia.

Rekaya Shabbir1, Conrado G Quiles1, Brian Lane1

  • 1Division of Cancer Sciences, University of Manchester, Manchester M20 4GJ, UK.

Cancers
|August 28, 2025
PubMed
Summary
This summary is machine-generated.

Investigating gene expression in hypoxic bladder cancer reveals more genes are upregulated at lower oxygen levels. This finding is crucial for developing new biomarkers for disease progression and prognosis in radioresistant cancers.

Keywords:
bladder cancerhypoxiasignature biomarkertranscriptome

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Hypoxic tumors are radioresistant, necessitating biomarkers to guide hypoxia-targeted therapies.
  • Current biomarkers often rely on gene expression data from cells exposed to 1% oxygen, potentially missing responses at lower, more heterogeneous tumor oxygen levels (<0.1%).

Purpose of the Study:

  • To investigate how different oxygen concentrations (0.1%, 0.2%, 1%, 20%) affect gene expression in bladder cancer cell lines.
  • To compare the prognostic capability of gene signatures identified at lower oxygen levels with existing signatures.
  • To identify novel hypoxia-responsive genes and pathways relevant to bladder cancer invasiveness and prognosis.

Main Methods:

  • Exposed four muscle-invasive bladder cancer (MIBC) and two non-MIBC cell lines to varying oxygen levels (0.1% to 20%) for 24 hours.
  • Analyzed transcriptomes using Clariom S microarrays to identify differentially expressed genes.
  • Compared the prognostic and predictive significance of a published 24-gene signature with a new signature derived from low-oxygen-identified genes.

Main Results:

  • The number of upregulated genes and involved biological pathways increased as oxygen levels decreased.
  • Seventy-seven genes were upregulated in at least three cell lines at 0.1% oxygen.
  • A 5-gene signature derived from low-oxygen-responsive genes showed similar prognostication to a 24-gene signature but did not predict treatment benefit.

Conclusions:

  • Gene expression responses to hypoxia in bladder cancer are oxygen-concentration dependent, with more genes upregulated at lower oxygen levels.
  • Differential gene expression between MIBC and NMIBC cells under hypoxia offers insights into bladder cancer invasiveness.
  • This study is the first to assess gene expression across multiple low-oxygen levels in bladder cancer to identify novel prognostic biomarkers.