27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth.

@article{Wu201327HydroxycholesterolPC,
  title={27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth.},
  author={Qian Wu and Tomonori Ishikawa and Rosa Sirianni and Hao Tang and Jeffrey G McDonald and Ivan S. Yuhanna and Bonne M. Thompson and Luc Girard and Chieko Mineo and Rolf A. Brekken and Michihisa Umetani and David M Euhus and Yang Xie and Philip W. Shaul},
  journal={Cell reports},
  year={2013},
  volume={5 3},
  pages={
          637-45
        }
}
To date, estrogen is the only known endogenous estrogen receptor (ER) ligand that promotes ER+ breast tumor growth. We report that the cholesterol metabolite 27-hydroxycholesterol (27HC) stimulates MCF-7 cell xenograft growth in mice. More importantly, in ER+ breast cancer patients, 27HC content in normal breast tissue is increased compared to that in cancer-free controls, and tumor 27HC content is further elevated. Increased tumor 27HC is correlated with diminished expression of CYP7B1, the… Expand
Estrogen Receptor Beta-Mediated Modulation of Lung Cancer Cell Proliferation by 27-Hydroxycholesterol
TLDR
It is found that 27HC promotes lung cancer cell proliferation in an estrogen receptor β (ERβ)-dependent manner and the effect was mediated by the PI3K-Akt signaling pathway, suggesting that lowering 27HC levels may lead to a novel approach for the treatment of lung cancer. Expand
The cholesterol metabolite 27-hydroxycholesterol regulates p53 activity and increases cell proliferation via MDM2 in breast cancer cells
TLDR
The results indicate that 27-OHC may contribute to ER-positive breast cancer progression by disrupting constitutive p53 signaling in an MDM2-dependent manner. Expand
The cholesterol metabolite 27-hydroxycholesterol stimulates cell proliferation via ERβ in prostate cancer cells
TLDR
The results show for the first time that 27-OHC, through ER activation, triggers deleterious effect in prostate cancer cell lines and it is proposed that dysregulated levels of 27- OHC may trigger or exacerbate prostate cancer via acting on ERβ. Expand
27-Hydroxycholesterol acts on myeloid immune cells to induce T cell dysfunction, promoting breast cancer progression.
TLDR
It is reported that 27HC impairs T cell expansion and cytotoxic function through its actions on myeloid cells, including macrophages, in a Liver X receptor (LXR) dependent manner, and pharmacologic inhibition of CYP27A1 reduced metastatic growth and improved the efficacy of checkpoint inhibitor, anti-PD-L1. Expand
Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness
TLDR
It is concluded that cholesterol and intratumoral accumulation of 27-HC promote the aggressive behavior process of PTC and targeting cholesterol metabolism could be a new therapeutic strategy in thyroid tumors with poor prognosis. Expand
Cholesterol synthesis inhibitor RO 48-8071 suppresses transcriptional activity of human estrogen and androgen receptor.
TLDR
It is shown that by real-time PCR analysis of mRNA from human breast cancer biopsies, no significant differences in OSC expression at various stages of disease, or between tumor and normal mammary cells, are shown. Expand
27-Hydroxycholesterol stimulates cell proliferation and resistance to docetaxel-induced apoptosis in prostate epithelial cells
TLDR
The results suggest that 27-OHC may play an important role in PCa and BPH progression by promoting proliferation and suppressing apoptosis. Expand
Breast cancer and (25R)-26-hydroxycholesterol
TLDR
Tamoxifen, an effective estrogen receptor antagonist that prevents breast cancer, also has the biologic property of blocking several steps in the lanosterol to cholesterol metabolic pathway, which may increase the amount of 27-hydroxycholesterol in breast tissue. Expand
The oncogenic roles of 27-hydroxycholesterol in glioblastoma
TLDR
Treatment with 27-HC promoted proliferation, epithelial to mesenchymal transition, colony formation, migration and invasion of U251 and U118 MG glioblastoma cells, and high levels of the metabolite were associated with poor outcome in patients. Expand
7-ketocholesterol and 27-hydroxycholesterol decreased doxorubicin sensitivity in breast cancer cells: estrogenic activity and mTOR pathway
TLDR
7-KC decreases the cytotoxicity of doxorubicin through the up-regulation of P-glycoprotein in an ERα- and mTOR-dependent pathway and could be reversed by inhibitors of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR). Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
27-hydroxycholesterol is an endogenous selective estrogen receptor modulator.
TLDR
It is demonstrated here that 27-hydroxycholesterol (27HC), the most prevalent oxysterol in circulation, functions as a SERM, the efficacy of which varies when assessed on different endpoints, and it appears that the unique pharmacological activity of 27HC relates to its ability to impact ER structure and modulate cofactor recruitment. Expand
Non-nuclear estrogen receptor alpha signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice.
TLDR
EDC is a non-nuclear selective ER modulator (SERM) in vivo, and in mice, non- nuclear ER signaling promotes cardiovascular protection and could be harnessed to provide vascular benefit without increasing the risk of uterine or breast cancer. Expand
The Cholesterol Metabolite 25-Hydroxycholesterol Activates Estrogen Receptor α-Mediated Signaling in Cancer Cells and in Cardiomyocytes
TLDR
It is demonstrated that the estrogen receptor (ER) α mediates gene expression changes and growth responses induced by 25HC in breast and ovarian cancer cells, and the estrogen-like activity of 25HC elicited in the cardiovascular system may play a role against hypoxic environments. Expand
Effect of Obesity on Breast Cancer Development
TLDR
This review explores the relationship between estrogen, estrogen receptors, and the adipokines leptin and adiponectin and the development of mammary cancer in humans and mouse models. Expand
27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen
TLDR
Increase in 27HC levels in mice by diet-induced hypercholesterolemia, pharmacologic administration or genetic manipulation decreased estrogen-dependent expression of vascular nitric oxide synthase and repressed carotid artery reendothelialization, indicating that 27HC functions as an endogenous selective estrogen receptor modulator (SERM). Expand
The oxysterol receptor LXR inhibits proliferation of human breast cancer cells.
The oxysterol receptors [liver X receptors (LXRalpha and LXRbeta)] regulate cholesterol and lipid biosynthesis and several studies link dysregulation of these metabolic pathways to aberrant cellExpand
Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice
TLDR
The hypothesis that postmenopausal obesity promotes tumor angiogenesis and breast cancer progression, possibly through increased adipose tissue mass and adipokines such as VEGF that could systemically and locally affect breast cancer progress, is supported. Expand
The estrogen receptor: a model for molecular medicine.
  • E. Jensen, V. Jordan
  • Medicine
  • Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2003
TLDR
A test was established to predict the outcome of antihormonal therapy in breast cancer, and a target was identified to develop new drugs for the treatment and prevention of breast cancer. Expand
Optimizing the antihormonal treatment and prevention of breast cancer
TLDR
The therapeutic options for anti-hormonal therapy, the role of anti-Hormonal agents in advanced breast cancer, and adjuvant therapy and the current status of chemoprevention with selective ER modulators are summarized. Expand
Obesity Accelerates Mouse Mammary Tumor Growth in the Absence of Ovarian Hormones
TLDR
Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones, which support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. Expand
...
1
2
3
4
...