Pregnancy Induces Persistent Changes that Potentiate Apoptotic Signaling and Responses to DNA Damage
Authors
Hagen, Mary J.Roberts, Amy L.
Dunphy, Karen A.
Blanchard, Jeffrey L.
Troester, Melissa A.
Schneider, Sallie S.
Jerry, D. Joseph
Document Type
Poster AbstractPublication Date
2013-05-08
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A full-term pregnancy reduces the lifetime risk of breast cancer by up to 50%. This effect is mediated, in part, by p53-dependent pathways. Gene expression profiling was used to investigate the mechanisms that alter apoptotic responses to DNA damage in the mammary gland. Radiation-induced responses in BALB/c-Trp53+/+ and BALB/c-Trp53-/- mice identified 121 genes that were altered by radiation and p53 status (p53-IR). To determine the effect of parity, mice were mated, force-weaned and mammary glands were allowed to involute for 21 days (parous) and compared with age-matched nulliparous mice. Gene expression profiles were determined in mammary tissues from nulliparous (N), parous (P), irradiated nulliparous (N-IR) and irradiated parous (P-IR) mice. The p53-IR gene signature did not differ among the N-IR and P-IR groups indicating that transcriptional activity of p53 was not altered by parity. However, expression profiles of apoptosis-related genes differed significantly in the parous group. The alterations in parous mammary tissues was accompanied by over-representation of biological processes that included “signal transduction” (e=1.69E-05). Within this set, Wnt signaling was especially pronounced (e Parity-regulated genes collaborate with p53-dependent targets, which act as a “switch”, to elicit apoptosis following ionizing radiation. The epigenetic states of the parity-regulated genes Tgfb2 and Wnt5a provide a mechanism for the persistent alterations in gene expression and apoptosis in parous mammary epithelial cells.DOI
10.13028/vm4p-7h97Permanent Link to this Item
http://hdl.handle.net/20.500.14038/27832Rights
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http://creativecommons.org/licenses/by-nc-sa/3.0/ae974a485f413a2113503eed53cd6c53
10.13028/vm4p-7h97