Pregnancy Induces Persistent Changes that Potentiate Apoptotic Signaling and Responses to DNA Damage Article Swipe

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Mary J. Hagen , Amy L. Roberts , Karen A. Dunphy , Jeffrey L. Blanchard , Melissa A. Troester , Sallie S. Schneider , D. Joseph Jerry ·

YOU? · · 2020 · Open Access · · DOI: https://doi.org/10.13028/vm4p-7h97

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.

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DNA damage Apoptosis Pregnancy Signal transduction Cell biology DNA Biology Chemistry Genetics

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Type: article
Language: en
Landing Page: https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1131&context=cts_retreat
OA Status: green
Related Works: 20
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DOI: https://doi.org/10.13028/vm4p-7h97

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Title: Pregnancy Induces Persistent Changes that Potentiate Apoptotic Signaling and Responses to DNA Damage

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Type: article

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Language: en

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Publication year: 2020

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Publication date: 2020-05-27

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Authors: Mary J. Hagen, Amy L. Roberts, Karen A. Dunphy, Jeffrey L. Blanchard, Melissa A. Troester, Sallie S. Schneider, D. Joseph Jerry

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Landing page: https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1131&context=cts_retreat

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Open access: Yes

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OA status: green

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OA URL: https://doi.org/10.13028/vm4p-7h97

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Concepts: DNA damage, Apoptosis, Pregnancy, Signal transduction, Cell biology, DNA, Biology, Chemistry, Genetics

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Cited by: 0

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Related works (count): 20

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