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Companion PowerPoint slide set Obesity-associated breast cancer risk: a role for epigenetics?

Companion PowerPoint slide set Obesity-associated breast cancer risk: a role for epigenetics?.

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Companion PowerPoint slide set Obesity-associated breast cancer risk: a role for epigenetics?

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  1. Companion PowerPoint slide set Obesity-associated breast cancer risk: a role for epigenetics? This teacher slide set was created by Dana Haine, MS, of the UNC Center for Environmental Health and Susceptibility, which is funded by the National Institute of Environmental Health Sciences (P30-ES010126).

  2. Dr. Liza Makowski Studies Basal-like Breast Cancer (BBC) • Aggressive cancer • No specific drug therapies • Short survival time if it spreads beyond breast tissue (metastasis) • More prevalent in young pre-menopausal women • More prevalent in African Americans • Obesity is a risk factor for all breast cancers

  3. Obesity causes BBC tumors to form at a faster ratecompared to lean mice Number of weeks until tumor formation Fat-fed (Lean) Fat-fed (obese)

  4. Cross-section of mammary (milk) duct http://www.womenshealth.gov/breast-cancer/what-is-breast-cancer/

  5. Label epithelial cells, fat cellsand fibroblasts on the diagram below: Inside (lumen) of milk duct

  6. Adipocytes (Fat cells) Fibroblasts Stroma of mammary tissue Epithelial Cells of Milk Duct Inside (lumen) of milk duct Immune cells are also present but are not shown in order to simplify schematic of the stroma.

  7. microenvironment

  8. HEALTHY CELL CANCER CELL Cancer & the microenvironment The microenvironment (“soil”) surrounding a cell (“seed”) plays a role in tumor formation. Liza Makowski: “How does obesity alter the microenvironment in breast cancer?”

  9. Cell to cell communication HGF-cMET paracrine signaling HGF C-met receptor Adapted from Melissa Troester/Patricia Casbas-Hernandez @ UNC

  10. Cell to cell communication HGF-cMET paracrine signaling HGF cMET receptor HGF P C-met Prevents cell death Promotes Cell Division Promotes growth of blood vessels to supply tumor Promotes motility (leads to Metastasis) Melissa Troester/Patricia Casbas-Hernandez @ UNC

  11. Obesity increases levels of HGF mRNA and protein in normal mammary tissue * Sundaram, S., Makowski, L., et. al. Cancer Prevention Research (Under Review, 2012)

  12. Ex vivo cell culture model Isolate Fibroblasts Culture Fibroblasts Measure Lean Mice HGF Secretion Normal Cell Division HGF Secretion Cancer- associated Obese Mice HGF Secretion HGF Secretion

  13. HGF secretion in cultured cells

  14. Isolate Fibroblasts Culture Fibroblasts HGF Secretion Lean Mice Normal Cancer- associated Obese Mice

  15. Analysis of c-Met protein levels in BBC tumor cell line BBC Tumor cell line + mHGF BBC Tumor cell line + CM BBC Tumor cell line C. Phospho-c-Met c-Met Control

  16. “How does obesity alter the microenvironment in breast cancer?” c-Met activation Signal HGF Secretion Epithelial cell Cancer formation Fat cell Fibroblast Microenvironment Conclusion: growth factor signaling pathway (HGF/cMet) was upregulated with obesity.

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