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Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer
- Source :
- Breast Cancer Research : BCR, Breast Cancer Research, Vol 21, Iss 1, Pp 1-18 (2019)
- Publication Year :
- 2019
- Publisher :
- BioMed Central, 2019.
-
Abstract
- Background A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood. Methods We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer. Results Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for
- Subjects :
- Biopsy
Notch signaling pathway
Breastfeeding
Estrogen receptor
Inflammation
Luminal progenitor cells
Breast Neoplasms
lcsh:RC254-282
Risk Assessment
Andrology
Abrupt involution
03 medical and health sciences
Mice
0302 clinical medicine
Breast cancer
Pregnancy
Risk Factors
Progesterone receptor
medicine
Animals
Humans
Lactation
Involution (medicine)
Hyperplasia
business.industry
Gene Expression Profiling
Epithelial Cells
Estrogens
Gene signature
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Flow Cytometry
Immunohistochemistry
3. Good health
Disease Models, Animal
Breast Feeding
Receptors, Estrogen
030220 oncology & carcinogenesis
Female
Steroids
Collagen
Disease Susceptibility
medicine.symptom
business
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1465542X and 14655411
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Breast Cancer Research : BCR
- Accession number :
- edsair.doi.dedup.....48df3c589732a5828e430ffc17a45f0d