Related Experiment Video

Updated: Aug 9, 2026

Methods to Evaluate Cytotoxicity and Immunosuppression of Combustible Tobacco Product Preparations
09:25

Methods to Evaluate Cytotoxicity and Immunosuppression of Combustible Tobacco Product Preparations

Published on: January 11, 2015

Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells

M G Cattaneo1, F D'atri, L M Vicentini

  • 1Department of Pharmacology, School of Medicine, University of Milano, Via Vanvitelli 32, 20129, Milano, Italy.

The Biochemical Journal
|January 24, 1998
PubMed

Insights

Nicotine stimulates mitogen-activated protein (MAP) kinase in small-cell lung carcinoma (SCLC) cells. This effect is indirect, involving a released factor that acts through specific cellular pathways.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Pharmacology

Background:

  • Nicotine is known to stimulate cell proliferation in small-cell lung carcinoma (SCLC) cell lines.
  • This stimulation is mediated by neuronal-type nicotinic receptors.

Purpose of the Study:

  • To investigate the mechanism by which nicotine stimulates mitogen-activated protein (MAP) kinase activity in SCLC cells.
  • To determine if the effect of nicotine on MAP kinase is direct or indirect.

Main Methods:

  • Utilized the GLC-8 SCLC cell line.
  • Measured MAP kinase activity in response to varying concentrations and durations of nicotine exposure.
  • Employed mecamylamine (neuronal nicotinic receptor antagonist), calcium-depleted media, pertussis toxin, and genistein (tyrosine kinase inhibitor).
  • Assessed the effect of cell-free supernatants from nicotine-stimulated cells on MAP kinase activity in recipient cells.

Main Results:

  • Nicotine stimulated MAP kinase activity in a concentration- and time-dependent manner (ED50 = 10 nM).
  • The effect was blocked by mecamylamine, indicating involvement of neuronal nicotinic receptors.
  • Inhibition of MAP kinase activity was observed with extracellular calcium absence, pertussis toxin, or genistein pretreatment.
  • Supernatants from nicotine-stimulated cells could activate MAP kinase in naive cells, but this effect was abolished if the recipient cells were pretreated with pertussis toxin or genistein.

Conclusions:

  • Nicotine indirectly stimulates MAP kinase in SCLC cells.
  • This indirect stimulation involves the release of a factor from nicotine-treated cells.
  • The released factor acts through a signaling pathway sensitive to pertussis toxin and tyrosine kinases, and dependent on extracellular calcium.

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition06:12

Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition

Published on: March 3, 2023

Related Concept Videos

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...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Drugs Acting on Autonomic Ganglia: Stimulants01:23

Drugs Acting on Autonomic Ganglia: Stimulants


Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...