Related Experiment Video
Updated: Oct 7, 2026
Growing Desmoplastic Three-Dimensional Pancreatic Cancer Spheroids from Co-Culture
Published on: September 27, 2024
FRAP-p70s6K signaling is required for pancreatic cancer cell proliferation
S A Shah1, M W Potter, R Ricciardi
1Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Background:
FRAP-p70s6K signaling regulates mitogenic responses to growth factors in eukaryotic cells. Constitutive p70s6K activation occurs in some human malignancies and may contribute to dysregulated cell growth. We examined whether inhibition of this pathway affects mitogen-induced proliferation and cell cycle progression of human pancreatic cancer cells in vitro.
Methods:
Quiescent BxPC3 and Panc-1 human pancreatic cancer cells treated with or without 20 ng/mL rapamycin (FRAP inhibitor) were repleted with 10% FCS to induce cell cycle entry. Proliferation was measured with MTT assay. Cell cycle and apoptosis were determined by FACS analysis. Phosphorylation of p70s6K, Akt, and cdc2 was evaluated by Western blot. Statistical analysis was by two-tailed t test (P < 0.05).
Results:
Rapamycin (Rapa) inhibited the phosphorylation of p70s6K while inducing G(1) cell cycle arrest (P < 0.005). In both cell lines, Rapa inhibited serum-induced proliferation (P < 0.05) without affecting apoptosis. Cdc2 phosphorylation was inhibited by 15 min with Rapa (not shown), consistent with cell cycle arrest. Akt phosphorylation was not affected, indicating FRAP specificity of Rapa.
Conclusions:
FRAP-p70s6K signaling appears to be necessary for G(1)-to-S phase progression and proliferation in pancreatic cancer cells. This supports earlier work demonstrating a similar regulatory role for PI-3' kinase, an upstream activator of FRAP-p70s6K.
Insights
Inhibition of FRAP-p70s6K signaling halts pancreatic cancer cell proliferation and G(1)-to-S phase progression. This pathway is crucial for mitogenic responses and tumor growth, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The FRAP-p70s6K signaling pathway regulates growth factor responses in cells.
- Aberrant p70s6K activation is implicated in human malignancies and uncontrolled cell growth.
- The role of this pathway in pancreatic cancer proliferation requires further investigation.
Purpose of the Study:
- To investigate the effect of inhibiting the FRAP-p70s6K pathway on pancreatic cancer cell proliferation.
- To determine if blocking this pathway impacts cell cycle progression in human pancreatic cancer cells.
Main Methods:
- Human pancreatic cancer cell lines (BxPC3, Panc-1) were treated with rapamycin (FRAP inhibitor) and serum.
- Proliferation was assessed using MTT assays.
- Cell cycle distribution, apoptosis, and protein phosphorylation (p70s6K, Akt, cdc2) were analyzed via FACS and Western blotting.
Main Results:
- Rapamycin effectively inhibited p70s6K phosphorylation and induced G(1) cell cycle arrest.
- Serum-induced proliferation was significantly reduced by rapamycin in both cell lines.
- Apoptosis was not affected, and Akt phosphorylation remained unchanged, confirming pathway specificity.
Conclusions:
- FRAP-p70s6K signaling is essential for G(1)-to-S phase transition and proliferation in pancreatic cancer cells.
- These findings align with the known regulatory role of PI-3' kinase in this pathway.
- Targeting FRAP-p70s6K signaling presents a potential therapeutic strategy for pancreatic cancer.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
01:19Interactions Between Signaling Pathways
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...