Related Experiment Video
Updated: Feb 28, 2026
10:36
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
11.0K
Estrogen Signaling During Abrupt Involution and Long-Term Metabolic Signature Similar to Estrogen Receptor-Negative
Kate Ormiston1, Neelam Shinde1, Gautam Sarathy1
1Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, USA.
International Journal of Molecular Sciences
|February 27, 2026
Summary
Lack of breastfeeding leads to abrupt involution (AI), increasing breast cancer risk by altering mammary gland metabolism and estrogen signaling. Gradual involution (GI) from breastfeeding shows different metabolic changes, highlighting key differences in cancer risk pathways.
Area of Science:
- Reproductive biology
- Cancer research
- Metabolic studies
Background:
- Epidemiological studies indicate a correlation between reduced breastfeeding and elevated breast cancer risk.
- Post-pregnancy breast tissue undergoes involution, a process significantly influenced by breastfeeding duration.
- Abrupt involution (AI), following no breastfeeding, contrasts with gradual involution (GI) from prolonged breastfeeding, with distinct metabolic and signaling implications.
Purpose of the Study:
- To investigate the metabolic differences in mammary gland adipocytes during abrupt involution (AI) versus gradual involution (GI).
- To explore how these metabolic changes during involution may contribute to increased breast cancer risk.
- To compare the metabolic profiles of AI and GI mammary glands with those of pregnancy-associated breast cancer (PABC).
Main Methods:
- Mouse models (FVB/n) were utilized, with pups removed to induce either AI (day 7) or GI (days 28 and 31).
- Mammary glands were collected at specific time points (days 28, 56, 120) for analysis.
- A subset of AI mice received tamoxifen treatment to assess its impact on metabolic phenotype.
Main Results:
- Day 28 AI mammary glands exhibited increased estrogen signaling, neutrophil activity, and glucose metabolism, alongside decreased adipogenesis and glycolysis compared to Day 56 GI glands.
- By Day 120, AI glands showed reduced oxidative phosphorylation and increased mitochondrial dysfunction, mirroring features of estrogen receptor-negative (ER-) PABC.
- Tamoxifen treatment in AI mice normalized the metabolic phenotype, bringing it closer to that of GI glands.
Conclusions:
- Early metabolic shifts in AI and GI mammary glands are potentially linked to estrogen signaling pathways.
- Long-term metabolic alterations in AI glands resemble those observed in breast cancer.
- Understanding these involution-associated metabolic changes is crucial for elucidating breast cancer risk factors.
More Related Videos
Related Concept Videos
01:01Autocrine Signaling
52.6K
Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
52.6K
01:45Endocrine Signaling
68.6K
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.6K