Growth regulation by estrogen in breast cancer 1 (GREB1) is a novel progesterone-responsive gene required for human endometrial stromal decidualization

Camden, Alison J.; Szwarc, Maria M.; Chadchan, Sangappa B.; DeMayo, Francesco J.; O’Malley, Bert W.; Lydon, John P.; Kommagani, Ramakrishna

doi:10.1093/molehr/gax045

Cited by 38 publications

(46 citation statements)

References 45 publications

(48 reference statements)

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“…Interestingly, SRC-3 is reported to interact with growth regulation by estrogen in breast cancer 1 (GREB1) and increase estrogen-induced transcription in breast cancer cell line MCF-7 cells [ 39 ]. We found that GREB1 is transcriptionally activated by SRC-2 via the progesterone–PR axis in endometrium [ 40 ], and a novel fusion gene, GREB1-SRC-2 , was detected in uterine sarcoma [ 41 ]. These evidences point out that GREB1 may play a vital role in hormone-dependent cancers.…”

Section: Nuclear Receptor Coactivators In Hormone-dependent Cancermentioning

confidence: 99%

“…GREB1 was first discovered in brain tissue [ 42 ] and later identified as an early estrogen-responsive gene in breast cancer [ 43 ]. The GREB1 gene is highly conserved across species and is expressed in many tissues, including the brain [ 42 ], mammary gland [ 43 ], ovary [ 16 ], prostate [ 44 ], and endometrium [ 40 ]. In humans, the GREB1 gene is located at 2p25.1, spans 108.68 kb, and contains 38 exons and 40 introns [ 43 , 45 ] ( Figure 2 ).…”

Section: Greb1 Structure and Functionmentioning

confidence: 99%

“…Third, throughout women’s reproductive years, GREB1 expression in the endometrium fluctuates in accordance with estrogen levels [ 59 ]. Fourth, GREB1 expression increased during progesterone-mediated endometrial stromal cell decidualization, and progesterone receptor knockdown led to a decrease in GREB1 transcript levels [ 40 ]. Further, three estrogen response elements (EREs) [ 54 , 58 ] and at least one androgen response element (ARE) [ 44 , 53 ] are located upstream of the GREB1 transcription start site ( Figure 2 ).…”

Section: Hormone Regulation Of Greb1mentioning

confidence: 99%

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Role for Growth Regulation by Estrogen in Breast Cancer 1 (GREB1) in Hormone-Dependent Cancers

Cheng

Michalski

Kommagani

2018

IJMS

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Sex hormones play important roles in the onset and progression of several cancers, such as breast, ovarian, and prostate cancer. Although drugs targeting sex hormone function are useful in treating cancer, tumors often develop resistance. Thus, we need to define the downstream effectors of sex hormones in order to develop new treatment strategies for these cancers. Recent studies unearthed one potential mediator of steroid hormone action in tumors: growth regulation by estrogen in breast cancer 1 (GREB1). GREB1 is an early estrogen-responsive gene, and its expression is correlated with estrogen levels in breast cancer patients. Additionally, GREB1 responds to androgen in prostate cancer cells, and can stimulate the proliferation of breast, ovarian, and prostate cancer cells. Recent studies have shown that GREB1 also responds to progesterone in human endometrial cells, suggesting that GREB1 is a pan steroid-responsive gene. This mini-review examines evidence that GREB1 participates in several hormone-dependent cancers and could be targeted to treat these cancers.

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Section: Nuclear Receptor Coactivators In Hormone-dependent Cancermentioning

confidence: 99%

Section: Greb1 Structure and Functionmentioning

confidence: 99%

Section: Hormone Regulation Of Greb1mentioning

confidence: 99%

See 1 more Smart Citation

Role for Growth Regulation by Estrogen in Breast Cancer 1 (GREB1) in Hormone-Dependent Cancers

Cheng

Michalski

Kommagani

2018

IJMS

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“…A very recent study on an independent clinical data set revealed that PGR expression is indeed correlated with BMI in endometrial cancer [16, 17]. GREB1 is essential for progesterone-driven endometrial decidualisation [18]. Hormone-targeted therapies are a common approach for advanced endometrial cancer and are more effective in patients with progesterone receptor positive tumours [19].…”

Section: Resultsmentioning

confidence: 99%

Gene expression profiling of The Cancer Genome Atlas supports an inverse association between body mass index (BMI) and major oesophageal tumour subtypes

Seim

Jeffery

Chopin

2018

Preprint

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In the last decade the Cancer Genome Atlas (TCGA) program has revealed significant insights into molecular events of dozens of cancers. These data sets are continuously updated, providing an unprecedented resource to the research community. There is now an emerging link between obesity and the development and progression of cancer. In this study we wished to identify genes related to body mass index (BMI) in TCGA datasets. Supporting epidemiological data, our gene expression profiling analyses suggest that oesophageal adenocarcinoma (EAC) can be considered a true obesity-associated cancer subtype, presenting avenues for prevention and treatment.

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“…Informed consent was obtained in accordance with a protocol approved by the Washington 151 Corporation, Carlsbad, USA) as described previously (Camden et al 2017 Sigma-Aldrich]). The EPC medium was changed every 48 hours until day six, when the cells were 177 harvested for RNA isolation with the total RNA isolation kit (Invitrogen/Life Technologies, Grand 178 Island, NY) or for protein isolation.…”

Section: Materials and Methods 149mentioning

confidence: 99%

The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization

Chadchan

Maurya

Popli

et al. 2020

Preprint

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29 STUDY QUESTION 30Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human 31 endometrium during the menstrual cycle, and does it participate in endometrial decidualization? 32 SUMMARY ANSWER 33 ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase 34 and is essential for human endometrial stromal cell decidualization. 35 WHAT IS KNOWN ALREADY 36ACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and 37 placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells. 38 STUDY DESIGN, SIZE, DURATION 39Proliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-40 age women and primary human endometrial stromal cells from proliferative phase endometrium 41 were used in the study. 42 PARTICIPANTS/MATERIALS, SETTING, METHODS 43ACE2 expression and localization were examined by qRT-PCR, Western blot, and 44 immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of 45 ACE2 knockdown on morphological and molecular changes of human endometrial stromal cell 46 decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone 47 to determine the effects of these hormones on ACE2 expression. 48 MAIN RESULTS AND THE ROLE OF CHANCE 49In human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the 50 proliferative phase of the menstrual cycle, and expression increases in stromal cells in the 51 secretory phase. The ACE2 mRNA (P ˂ 0.0001) and protein abundance increased during primary 52 human endometrial stromal cell (HESC) decidualization. HESCs transfected with ACE2-targeting 53 siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change 54 and lower expression of the decidualization markers PRL and IGFBP1 (P ˂ 0.05). In mice during 55 pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through 56 day six of pregnancy. Finally, progesterone induced expression of Ace2 mRNA in mouse uteri 57 more than vehicle or estrogen (P ˂ 0.05). 58 LIMITATIONS, REASONS FOR CAUTION 61Experiments assessing the function of ACE2 in human endometrial stromal cell decidualization 62 were in vitro. Whether SARS-CoV-2 can enter human endometrial stromal cells and affect 63 decidualization have not been assessed. 64 WIDER IMPLICATIONS OF THE FINDINGS 65Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and 66 stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. 67If so, women with COVID-19 may be at increased risk of early pregnancy loss. 68 STUDY FUNDINGS/COMPETING INTEREST(S)

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Growth regulation by estrogen in breast cancer 1 (GREB1) is a novel progesterone-responsive gene required for human endometrial stromal decidualization

Cited by 38 publications

References 45 publications

Role for Growth Regulation by Estrogen in Breast Cancer 1 (GREB1) in Hormone-Dependent Cancers

Role for Growth Regulation by Estrogen in Breast Cancer 1 (GREB1) in Hormone-Dependent Cancers

Gene expression profiling of The Cancer Genome Atlas supports an inverse association between body mass index (BMI) and major oesophageal tumour subtypes

The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization

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