Epidermal Growth Factor Induction of Phenotype-dependent Cell Cycle Arrest in Vascular Smooth Muscle Cells Is through the Mitogen-activated Protein Kinase Pathway
Bibliographic record
Abstract
The heterogeneity of vascular smooth muscle cells is well established in tissue culture, but their differential responses to growth factors are not completely defined. We wished to identify effects of epidermal growth factor (EGF) on vascular smooth muscle cells in distinct phenotypes, such as spindle and epithelioid. We found that the EGF receptors were abundant in epithelioid cells but not spindle cells. EGF treatment inhibited serum-independent DNA synthesis, which was absent in spindle cells, of epithelioid cells. Additionally, using a pulse-chase assay, we found that bromodeoxyuridine-labeled cells failed to re-enter the S phase in the presence of EGF. These EGF effects were abolished by either inhibiting the EGF receptor tyrosine kinase with AG1478 or inhibiting the mitogen-activated protein kinase pathway with PD98059. In response to treatment with EGF, the EGF receptor was phosphorylated, which was correlated with phosphorylation and activation of p42/44 mitogen-activated protein kinases. Inhibition of EGF receptor phosphorylation and mitogen-activated protein kinase activation resulted in a reversal of the EGF-induced inhibition of bromodeoxyuridine incorporation and cell cycle arrest. Subsequent studies revealed that the activation of the EGF receptor and the mitogen-activated protein kinase pathway in epithelioid cells induced expression of the cell cycle inhibitory protein p27Kip1 but not p21Cip1. Taken together, our data demonstrate that the EGF receptor is abundantly expressed in epithelioid vascular smooth muscle cells and that the activation of this receptor results in cell cycle arrest through activation of the mitogen-activated protein kinase pathway.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".