{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:37:22Z","timestamp":1787618242767,"version":"build-2736575974"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA231875"],"award-info":[{"award-number":["R01CA231875"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32CA229114"],"award-info":[{"award-number":["T32CA229114"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ohio State University Medical Center Comprehensive Cancer Center Breast Cancer Young Investigator Award","award":["#GR131265"],"award-info":[{"award-number":["#GR131265"]}]},{"name":"Pelotonia Postdoctoral Fellowship"},{"name":"NIH","award":["R01R01DK133859-01A1"],"award-info":[{"award-number":["R01R01DK133859-01A1"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Epidemiological data link a lack of breastfeeding with an increased risk of breast cancer. Breast tissue remodels after pregnancy through involution. Long-term breastfeeding results in gradual involution (GI), and a lack of breastfeeding leads to abrupt involution (AI). AI causes increased mammary gland estrogen signaling, causing adipocyte redifferentiation through neutrophil infiltration. Adipocyte differences and metabolic implications of involution have not been explored between AI and GI. As breast cancer is characterized as highly metabolic, we explored how adipocyte differences and metabolism during involution may support breast cancer risk. FVB\/n was randomized to AI\/GI and standardized to 6 pups on day 0\/birth. AI mice had pups removed on day 7. GI mice had 3 pups removed on days 28 and 31. Mammary glands were harvested at 28, 56, and 120 days. A subset of AI mice were given tamoxifen for 21 days. Day 28 AI glands had upregulation of estrogen signaling, neutrophil degranulation, and glucose metabolism and downregulation of adipogenesis and glycolysis compared to Day 56 GI. Day 120 AI glands had downregulation of oxidative phosphorylation and upregulation of mitochondrial dysfunction similar to estrogen receptor-negative (ER\u2212) pregnancy-associated breast cancer (PABC). AI with tamoxifen resulted in a similar metabolic phenotype to GI. Early metabolic phenotypes in AI and GI glands may be related to estrogen signaling. AI long-term transcriptional metabolic effects were similar to breast cancer.<\/jats:p>","DOI":"10.3390\/ijms27041951","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:45:58Z","timestamp":1771415158000},"page":"1951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Estrogen Signaling During Abrupt Involution and Long-Term Metabolic Signature Similar to Estrogen Receptor-Negative Breast Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-8180","authenticated-orcid":false,"given":"Kate","family":"Ormiston","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Shinde","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Sarathy","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajni","family":"Shukla","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Alsammerai","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annapurna","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djawed","family":"Bennouna","sequence":"additional","affiliation":[{"name":"Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wesolowski","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Nursing, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Kopec","sequence":"additional","affiliation":[{"name":"Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eswar","family":"Shankar","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-7746","authenticated-orcid":false,"given":"Kristin","family":"Stanford","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, Department of Surgery, Division of General and Gastrointestinal Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Ganju","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarmila","family":"Majumder","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvaneswari","family":"Ramaswamy","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Stover","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","unstructured":"(2025, October 05). 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