ArticleMolecular and cellular biology2004
Upregulation of the Catalytic Telomerase Subunit by the Transcription Factor ER81 and Oncogenic HER2/Neu, Ras, or Raf.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 126 citations in OpenAlex.
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Phytocompounds-based therapeutic approach: Investigating curcumin and green tea extracts on MCF-7 breast cancer cell line.Journal, genetic engineering & biotechnology · 2024Article
- Association of hTERT expression, Her2Neu, estrogen receptors, progesterone receptors, with telomere length before and at the end of treatment in breast cancer patients.Frontiers in medicine · 2024Article
- Identification of mechanism of cancer-cell-specific reactivation of hTERT offers therapeutic opportunities for blocking telomerase specifically in human colorectal cancer.Nucleic acids research · 2023Article
- Methylation of the epigenetic JMJD2D protein by SET7/9 promotes prostate tumorigenesis.Frontiers in oncology · 2023Article
- Methylation of the JMJD2B epigenetic regulator differentially affects its ability to coactivate the ETV1 and JUN transcription factors.International journal of biochemistry and molecular biology · 2023Article
- Promotion of colorectal cancer by transcription factor BHLHE40 involves upregulation ofFrontiers in oncology · 2023Article
- An inducible CRISPR/Cas9 screen identifies DTX2 as a transcriptional regulator of human telomerase.iScience · 2022Article
- Sumoylation of transcription factor ETV1 modulates its oncogenic potential in prostate cancer.International journal of clinical and experimental pathology · 2021Article
- Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer.International journal of oncology · 2020Article
- Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer.Methods and protocols · 2020Article
- Telomerase as a Possible Candidate Targeting Therapy in Different Breast Cancer Cell Lines.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Relationship between ETS Transcription Factor ETV1 and TGF-β-regulated SMAD Proteins in Prostate Cancer.Scientific reports · 2019Article
- A potential common role of the Jumonji C domain-containing 1A histone demethylase and chromatin remodeler ATRX in promoting colon cancer.Oncology letters · 2018Article
- Current Insights to Regulation and Role of Telomerase in Human Diseases.Antioxidants (Basel, Switzerland) · 2017Review
- Transcriptional Regulation of Telomerase Reverse Transcriptase (TERT) by MYC.Frontiers in cell and developmental biology · 2017Review
- Telomerase Regulation from Beginning to the End.Genes · 2016Review
- Review
- ETS transcription factor ERG cooperates with histone demethylase KDM4A.Oncology reports · 2016Article
- Telomerase activity in breast cancer patients: association with poor prognosis and more aggressive phenotype.Medical oncology (Northwood, London, England) · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
One hallmark of tumor formation is the transcriptional upregulation of human telomerase reverse transcriptase, hTERT, and the resultant induction of telomerase activity. However, little is presently understood about how hTERT is differentially activated in tumor cells versus normal somatic cells. Specifically, it is unclear if oncoproteins can directly elicit hTERT expression. To this end, we now show that three oncoproteins, HER2/Neu, Ras, and Raf, stimulate hTERT promoter activity via the ETS transcription factor ER81 and ERK mitogen-activated protein (MAP) kinases. Mutating ER81 binding sites in the hTERT promoter or suppression of ERK MAP kinase-dependent phosphorylation of ER81 rendered the hTERT promoter unresponsive to HER2/Neu. Further, expression of dominant-negative ER81 or inhibition of HER2/Neu significantly attenuated telomerase activity in HER2/Neu-overexpressing SKBR3 breast cancer cells. Moreover, HER2/Neu, Ras, and Raf collaborated with ER81 to enhance endogenous hTERT gene transcription and telomerase activity in hTERT-negative, nonimmortalized BJ foreskin fibroblasts. Accordingly, hTERT expression was increased in HER2/Neu-positive breast tumors and breast tumor cell lines relative to their HER2/Neu-negative counterparts. Collectively, our data elucidated a mechanism whereby three prominent oncoproteins, HER2/Neu, Ras, and Raf, may facilitate tumor formation by inducing hTERT expression in nonimmortalized cells via the transcription factor ER81.
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