ArticleThe Journal of biological chemistry2012
Transcription factors Sp1 and p73 control the expression of the proapoptotic protein NOXA in the response of testicular embryonal carcinoma cells to cisplatin.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- Molecular pathology of testicular germ cell tumours: an update for practicing pathologists.Histopathology · 2026Review
- Overcoming Chemotherapy Resistance in Germ Cell Tumors.Biomedicines · 2022Review
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- APR-246 induces apoptosis and enhances chemo-sensitivity via activation of ROS and TAp73-Noxa signal in oesophageal squamous cell cancer with TP53 missense mutation.British journal of cancer · 2021Article
- The Enigmatic Role of TP53 in Germ Cell Tumours: Are We Missing Something?International journal of molecular sciences · 2021Review
- Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells-Relevance for Understanding (Germ Cell) Tumorigenesis.International journal of molecular sciences · 2021Review
- Article
- Pro-death signaling of cytoprotective heat shock factor 1: upregulation of NOXA leading to apoptosis in heat-sensitive cells.Cell death and differentiation · 2020Article
- Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives.Cancers · 2020Review
- Induction of p53-Dependent Apoptosis by Prostaglandin ABiomolecules · 2020Article
- p53-Related Transcription Targets of TAp73 in Cancer Cells-Bona Fide or Distorted Reality?International journal of molecular sciences · 2020Review
- Review
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Molecular Mechanisms of Cisplatin Chemoresistance and Its Circumventing in Testicular Germ Cell Tumors.Current oncology reports · 2018Review
- Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage.Nucleic acids research · 2018Article
- Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway.Molecular medicine reports · 2018Article
- Exploring the molecular aspects associated with testicular germ cell tumors: a review.Oncotarget · 2018Review
- Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.Oncogene · 2017Article
- Sall2 is required for proapoptotic Noxa expression and genotoxic stress-induced apoptosis by doxorubicin.Cell death & disease · 2015Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Testicular germ cell tumors (TGCTs) are highly responsive to and curable by cisplatin-based chemotherapy even in advanced stages. We have studied the molecular mechanisms involved in the induction of apoptosis in response to cisplatin, and found that proapoptotic Noxa is transcriptionally up-regulated following cisplatin exposure, even in the absence of p53, in NTERA2 cisplatin-sensitive cells but not in 1411HP-resistant cells. Blockade of Noxa reduced the apoptotic response of embryonal carcinoma (EC) NTERA2 cells to cisplatin. A detailed analysis of the Noxa promoter revealed that p73 and Sp1-like factors, Sp1 and KLF6, played key roles in the transcriptional control of this gene. Overexpression of TAp73 induced Noxa whereas the dominant negative isoform ΔNp73, reduced the levels of Noxa after cisplatin exposure in NTERA2 and 2102EP. Interestingly, down-regulation of Sp1 increased Noxa expression in response to cisplatin. However, blockade of KLF6 decreased cisplatin-induced up-regulation of Noxa in EC cell lines. In addition, tissue microarray analyses of TGCTs revealed that expression of Noxa correlates with good clinical prognosis in patients with embryonal carcinoma. Thus, our data show the transcriptional network that regulates Noxa in EC cells, which is key for their apoptotic response to cisplatin-based chemotherapy, and propose Noxa as a predictive factor of therapeutic response.
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