Aging-associated Increase in Expression of Tumor Suppressor Genes in the Colon Epithelium

Undergraduate #19
Discipline: Biological Sciences
Subcategory: Cancer Research

Karla Batres Gonzalez - Johnson C. Smith University
Co-Author(s): Alyssa Luck, Eric Blue, Elle Glenny, Emily Moorefield, and P. Kay Lund, University of North Carolina at Chapel Hill, Chapel Hill, NC

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Stem cells of the colon continually replenish the colonic epithelium. The risk of colon cancer increases with age, as cells accumulate damage from pro-cancer agents. The expression levels of certain genes indicate whether there are irregularities in proliferation, apoptosis or DNA damage. Damaged DNA can trigger the cell to repair, enter cell cycle arrest or undergo apoptosis. However, some oncogenic mutations disrupt these corrective mechanisms, leading to tumor initiation, progression, or metastasis. Aging leads to dysregulation of the cell cycle through uncontrolled proliferation or cell cycle checkpoints resulting in increased cancer risk. Immunofluorescence, gene expression and protein expression analyses were performed on isolated colonic epithelial cells to asses markers of proliferation, cell cycle regulation, apoptosis and stem cells in young and old mice. Aging results in increased colonic epithelial cell expression of tumor suppressor genes p53 and p16 and a trend for Chk1 in the colonic epithelium of aged mice. However, no changes in markers of proliferation (EdU incorporation or Ccnd1 expression), apoptosis (Bax or PARP expression) or DNA damage (γ-H2AX expression) were observed between young and old mice. There were also no significant difference in the expression of stem cell genes (Lgr5 and Sox9) in the colonic epithelium of young mice compared to old mice. Aging leads to increased expression of tumor suppressor genes p53 and p16 in the colonic epithelium. An increase of tumor suppressor gene expression does not correlate with changes in proliferation, DNA damage or apoptosis in the colonic epithelium but may promote protection against senescence or oncogenic mutations.

Funder Acknowledgement(s): This project was supported by the SPIRE program, an IRACDA grant from the Training, Workforce Development & Diversity branch of NIGMS/NIH (K12GM000678) and NIH R01-AG041198 (PKL). Input from the intestinal stem cell group is acknowledged (Scott Magness, Chris Dekaney and Susan Henning).

Faculty Advisor: Emily Moorefield,