ArticleCancer research2008
HEXIM1 regulates 17beta-estradiol/estrogen receptor-alpha-mediated expression of cyclin D1 in mammary cells via modulation of P-TEFb.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- cGAS/STING-Independent Induction of Type I Interferon by Inhibitors of the Histone Methylase KDM5B.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1.Endocrinology · 2022Article
- Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells.Breast cancer research : BCR · 2019Article
- Phosphorylation of the histone demethylase KDM5B and regulation of the phenotype of triple negative breast cancer.Scientific reports · 2019Article
- HMBA is a putative HSP70 activator stimulating HEXIM1 expression that is down-regulated by estrogen.The Journal of steroid biochemistry and molecular biology · 2017Article
- Induction of HEXIM1 activities by HMBA derivative 4a1: Functional consequences and mechanism.Cancer letters · 2016Article
- Functional Interaction between HEXIM and Hedgehog Signaling during Drosophila Wing Development.PloS one · 2016Article
- SUPT6H controls estrogen receptor activity and cellular differentiation by multiple epigenomic mechanisms.Oncogene · 2015Article
- Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.Cancer biology & therapy · 2015Article
- HEXIM1 plays a critical role in the inhibition of the androgen receptor by anti-androgens.The Biochemical journal · 2014Article
- Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy.Cellular and molecular life sciences : CMLS · 2014Article
- Lead optimization of HMBA to develop potent HEXIM1 inducers.Bioorganic & medicinal chemistry letters · 2014Article
- HEXIM1 down-regulates hypoxia-inducible factor-1α protein stability.The Biochemical journal · 2013Article
- Inhibition of metastasis by HEXIM1 through effects on cell invasion and angiogenesis.Oncogene · 2013Article
- Inducible re-expression of HEXIM1 causes physiological cardiac hypertrophy in the adult mouse.Cardiovascular research · 2013Article
- Pausing for thought: disrupting the early transcription elongation checkpoint leads to developmental defects and tumourigenesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2013Article
- Derailed estrogen signaling and breast cancer: an authentic couple.Endocrine reviews · 2013Review
- Complex effects of flavopiridol on the expression of primary response genes.Cell division · 2012Article
- Serum HER2/ECD value in stage I and II early breast cancer: need of a lower cut-off?Wiener klinische Wochenschrift · 2011Article
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Estrogen receptor alpha (ERalpha) plays a key role in mammary gland development and is implicated in breast cancer through the transcriptional regulation of genes linked to proliferation and apoptosis. We previously reported that hexamethylene bisacetamide inducible protein 1 (HEXIM1) inhibits the activity of ligand-bound ERalpha and bridges a functional interaction between ERalpha and positive transcription elongation factor b (P-TEFb). To examine the consequences of a functional HEXIM1-ERalpha-P-TEFb interaction in vivo, we generated MMTV/HEXIM1 mice that exhibit mammary epithelial-specific and doxycycline-inducible expression of HEXIM1. Increased HEXIM1 expression in the mammary gland decreased estrogen-driven ductal morphogenesis and inhibited the expression of cyclin D1 and serine 2 phosphorylated RNA polymerase II (S2P RNAP II). In addition, increased HEXIM1 expression in MCF-7 cells led to a decrease in estrogen-induced cyclin D1 expression, whereas down-regulation of HEXIM1 expression led to an enhancement of estrogen-induced cyclin D1 expression. Studies on the mechanism of HEXIM1 regulation on estrogen action indicated a decrease in estrogen-stimulated recruitment of ERalpha, P-TEFb, and S2P RNAP II to promoter and coding regions of ERalpha-responsive genes pS2 and CCND1 with increased HEXIM1 expression in MCF-7 cells. Notably, increased HEXIM1 expression decreased only estrogen-induced P-TEFb activity. Whereas there have been previous reports on HEXIM1 inhibition of P-TEFb activity, our studies add a new dimension by showing that E(2)/ER is an important regulator of the HEXIM1/P-TEFb functional unit in breast cells. Together, these studies provide novel insight into the role of HEXIM1 and ERalpha in mammary epithelial cell function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.