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Related Concept Videos

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.
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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...
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...
Inhibition of Cdk Activity02:34

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
The Intrinsic Apoptotic Pathway01:31

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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

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Expression profiling identifies three pathways altered in cellular immortalization: interferon, cell cycle, and

Aviva Levine Fridman1, Lin Tang, Olga I Kulaeva

  • 1Program in Molecular Biology and Human Genetics, Barbara Ann Karmanos Cancer Institute, and Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 110 East Warren Ave., Detroit, Michigan 48201, USA.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|September 9, 2006
PubMed
Summary

Cellular senescence abrogation is key to cancer development. This study identified interferon, cell cycle, and cytoskeletal genes involved in immortalization, offering insights into cancer and aging molecular targets.

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Analysis of Cell Cycle Position in Mammalian Cells
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Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cellular senescence is a barrier to tumorigenesis, and its abrogation leads to cell immortalization.
  • Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome often associated with cellular immortalization.
  • Epigenetic silencing, particularly via DNA methylation, is implicated in regulating gene expression during cellular processes.

Purpose of the Study:

  • To investigate gene expression changes associated with spontaneous immortalization in Li-Fraumeni syndrome (LFS) cell lines.
  • To identify genes and pathways epigenetically silenced by promoter methylation that may regulate senescence and immortalization.
  • To understand the molecular mechanisms underlying cellular immortalization and its relevance to cancer and aging.

Main Methods:

  • Utilized four independent, spontaneously immortalized LFS cell lines.
  • Induced a senescence-like phenotype in immortal LFS cells using 5-aza-deoxycytidine, a DNA methyltransferase (DNMT) inhibitor.
  • Employed microarrays to compare epigenetic gene expression profiles between precrisis and immortal LFS cells.
  • Performed gene ontology analysis on expression data.

Main Results:

  • Gene expression profiling revealed significant alterations in interferon pathway, cell cycle, and cytoskeletal genes during immortalization.
  • Identified potential epigenetic regulation by DNA methylation in key genes controlling senescence and immortalization.
  • Demonstrated that inhibiting DNA methyltransferase can re-induce a senescence-like phenotype in immortalized cells.

Conclusions:

  • Epigenetically silenced genes, particularly those in the interferon pathway, cell cycle, and cytoskeleton, play a crucial role in cellular immortalization.
  • Understanding these regulatory genes and pathways provides insights into the fundamental processes of aging and cancer development.
  • This research identifies potential molecular targets for therapeutic interventions in cancer and age-related diseases.