Obesity and p16 INK4A Downregulation Activate Breast Adipocytes and Promote Their Protumorigenicity
Al-Khalaf HH., Amir M., Al-Mohanna F., Tulbah A., Al-Sayed A., Aboussekhra A.
Laboratory Study, published in Mol Cell Biol (2017) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Laboratory Study
- Journal
- Mol Cell Biol (2017)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 28630279
- PMCID
- PMC5559683
- DOI
- 10.1128/mcb.00101-17
- Citations
- 12
Abstract (original English)
Obesity is increasingly recognized as a risk factor for breast cancer development. However, the molecular basis of obesity-related breast carcinogenesis remains elusive. In this study, we have shown that obesity reduces the level of the tumor suppressor p16 INK4A protein in breast adipocytes, which showed active features and strong procarcinogenic potential both in vitro and in orthotopic tumor xenografts compared to mature adipocytes from lean women. Furthermore, obesity triggered epithelial-to-mesenchymal transition (EMT) in breast ductal epithelial cells. Interestingly, specific downregulation of p16 INK4A increased the expression/secretion levels of various adipokines, including leptin, and activated breast adipocytes from lean women. Consequently, like breast adipocytes from obese women, p16-deficient adipocytes induced EMT in normal primary breast luminal cells in a leptin-dependent manner and enhanced tumor growth. Additionally, we have shown that p16 INK4A negatively controls leptin at the mRNA level through microRNAs 141 and 146b-5p (miR-141 and miR-146b-5p), which bind the leptin mRNA at a specific sequence in the 3' untranslated region (UTR). These results show that obesity activates breast stromal adipocytes through p16 downregulation, which upregulates leptin and promotes procarcinogenic processes.
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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