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Cited by 15PI3K/AKT/mTOR signaling in cancerBreast Cancer Treatment StudiesDevelopmental Biology and Gene Regulation

PTEN is required to maintain luminal epithelial homeostasis and integrity in the adult mammary gland

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Shore, Amy N., Chang, Chi-Hsuan, Kwon, Oh-Joon, Weston, Matthew C., Zhang, Mei, Xin, Li, Rosen, Jeffrey M.·2016·Developmental Biology
DOI 10.1016/j.ydbio.2015.10.023PMC PMC4688181
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Abstract

In the mammary gland, PTEN loss in luminal and basal epithelial cells results in differentiation defects and enhanced proliferation, leading to the formation of tumors with basal epithelial characteristics. In breast cancer, PTEN loss is associated with a hormone receptor-negative, basal-like subtype that is thought to originate in a luminal epithelial cell. Here, we show that luminal-specific PTEN loss results in distinct effects on epithelial homeostasis and mammary tumor formation. Luminal PTEN loss increased proliferation of hormone receptor-negative cells, thereby decreasing the percentage of hormone receptor-positive cells. Moreover, luminal PTEN loss led to misoriented cell divisions and mislocalization of cells to the intraluminal space of mammary ducts. Despite their elevated levels of activated AKT, Pten-null intraluminal cells showed increased levels of apoptosis. One year after Pten deletion, the ducts had cleared and no palpable mammary tumors were detected. These data establish PTEN as a critical regulator of luminal epithelial homeostasis and integrity in the adult mammary gland, and further show that luminal PTEN loss alone is not sufficient to promote the progression of mammary tumorigenesis.

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  • p63 and PTEN are tumor suppressors that play a key role in breast and prostate tissue development.

    “we inhibited p63 and PTEN expression, two genes that are described as tumor-suppressors that play a key role in breast and prostate tissue development (32–35).”

    From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [32]

    The Introduction (page not provided) identifies PTEN as a tumor suppressor and describes its role in mammary epithelial development; it also discusses effects of PTEN loss in the prostate. The paper does not establish the corresponding claim about p63, so it supports only the PTEN portion of the statement attributed to the citation group. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Shore, A. N., Chang, C.-H., Kwon, O.-J., Weston, M. C., Zhang, M., Xin, L., & Rosen, J. M.
Affiliations
  • Baylor College of Medicine (US)
  • University of Pittsburgh (US)
Corresponding author
Shore, Amy N.
ORCID
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2016-01
Volume
409
Issue
1
Pages
202-217
ISSN
0012-1606 (ISSN-L)
DOI
10.1016/j.ydbio.2015.10.023
PMC
PMC4688181
OpenAlex
W2194460350
Cited by
15
References
5
Citations by year
2025: 3 · 2024: 1 · 2023: 1 · 2021: 1 · 2019: 2 · 2018: 3 · 2017: 4
FWCI
0.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH
  • Eunice Kennedy Shriver National Institute of Child Health & Human Development
  • National Cancer Institute
  • NINDS (NS087095)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
PTEN, mammary gland, luminal epithelium, epithelial homeostasis, mammary tumor formation, basal-like breast cancer, cell proliferation, Akt activation, apoptosis, mammary ducts, tumor suppression
MeSH terms
Aging, Animals, Cell Adhesion, Cell Differentiation, Cell Division, Epithelial Cells, Epithelium, Female, Homeostasis, Mammary Glands, Animal, Spindle Apparatus, Receptors, Progesterone, Tamoxifen, Signal Transduction, Cell Polarity, Apoptosis, Mice, Knockout, Integrases, Cell Proliferation, PTEN Phosphohydrolase, Keratin-8, TOR Serine-Threonine Kinases

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