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Increased pro-inflammatory mediators leads to Increase, Cell Proliferation (Epithelial Cells)
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer||adjacent||Moderate||Not Specified||Evgeniia Kazymova (send email)||Under development: Not open for comment. Do not cite||Under Development|
|Increased DNA damage leading to increased risk of breast cancer||adjacent||Moderate||Not Specified||Allie Always (send email)||Under development: Not open for comment. Do not cite||Under Development|
Life Stage Applicability
Key Event Relationship Description
Pro-inflammatory factors increase proliferation.
Evidence Collection Strategy
Evidence Supporting this KER
Biological Plausibility is High. Inflammation is generally understood to lead to proliferation during recovery from inflammation.
Biological Plausibility is High. Inflammation is generally understood to lead to proliferation during recovery from inflammation. Major inflammation-related transcription factors NF-kB, AP1, and STAT3 mediate proliferation and survival (Grivennikov, Greten et al. 2010). Inflammation enhances compensatory proliferation during wound healing including following inflammation-associated cell killing (Landen, Li et al. 2016), and contributes to proliferation via growth enhancing signals including changes to the microenvironment and promotion of stem-like characteristics (Grivennikov, Greten et al. 2010; Hanahan and Weinberg 2011; Kiraly, Gong et al. 2015). These effects can vary between tissues and in different contexts in ways that are not well understood (Grivennikov, Greten et al. 2010). In mammary gland and in mammary epithelial cells, inflammation-related transcription factor NF-kB and multiple cytokines promote proliferation and tumorigenesis (Connelly, Barham et al. 2011; Esquivel-Velazquez, Ostoa-Saloma et al. 2015).