Publications by authors named "Pekka T Heikkinen"

Article Synopsis
  • - The study evaluated a multiplexed in vitro genotoxicity assay called the MultiFlow DNA Damage Kit, which uses flow cytometry to analyze DNA damage in cells and categorize chemicals based on their genotoxic effects.
  • - Conducted across seven laboratories, the assay tested 84 reference chemicals and involved exposure of TK6 cells, followed by flow cytometric analysis to determine the predominant mode of action (MoA) of the chemicals.
  • - Results showed high sensitivity, specificity, and agreement (≥ 92%) across different labs, indicating that this assay can effectively and reliably classify new chemicals' genotoxic potentials using either of the two proposed data analysis strategies.
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The receptor-tyrosine kinase ErbB4 was identified as a direct regulator of hypoxia-inducible factor-1α (HIF-1α) signaling. Cleaved intracellular domain of ErbB4 directly interacted with HIF-1α in the nucleus, and stabilized HIF-1α protein in both normoxic and hypoxic conditions by blocking its proteasomal degradation. The mechanism of HIF stabilization was independent of VHL and proline hydroxylation but dependent on RACK1.

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Smad7 is an inhibitor of the transforming growth factor-beta-activated signaling pathway. Under well-oxygenated conditions, Smad7 is a potent inhibitor of carcinoma cell invasion. Paradoxically, however, the expression of Smad7 is upregulated across several cancers and may promote cancer progression.

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The transforming growth factor-beta (TGF-beta) maintains epithelial homeostasis and suppresses early tumor formation, but paradoxically at later stages of tumor progression, TGF-beta promotes malignancy. TGF-beta activates phosphorylation of Smad2 and -3 effectors. Smad2 and -3 are known to have different functions, but differential regulation of their phosphorylation has not been described.

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