ArticleProceedings of the National Academy of Sciences of the United States of America1993
Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 149 citations in OpenAlex.
- Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer.British journal of cancer · 2006Trial
- Investigating the role of cathepsins in breast cancer progression: a Mendelian randomization study.Frontiers in oncology · 2025Article
- Cathepsin D is essential for the degradomic shift of macrophages required to resolve liver fibrosis.Molecular metabolism · 2024Article
- Comparative differential cytotoxicity of clinically used SERMs in human cancer lines of different origin and its predictive molecular docking studies of key target genes involved in cancer progression and treatment responses.Current research in pharmacology and drug discovery · 2022Article
- Cathepsin D-Managing the Delicate Balance.Pharmaceutics · 2021Review
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- Review
- A novel bis-aryl urea compound inhibits tumor proliferation via cathepsin D-associated apoptosis.Anti-cancer drugs · 2020Article
- Article
- Cation-dependent mannose-6-phosphate receptor expression and distribution are influenced by estradiol in MCF-7 breast cancer cells.PloS one · 2018Article
- Two Faces of Cathepsin D: Physiological Guardian Angel and Pathological Demon.Biology and medicine (Aligarh) · 2014Article
- Support of a bi-faceted role of estrogen receptor β (ERβ) in ERα-positive breast cancer cells.Endocrine-related cancer · 2014Article
- Transcriptional regulation of proteoglycan 4 by 17β-estradiol in immortalized baboon temporomandibular joint disc cells.European journal of oral sciences · 2014Article
- Statistical significance of combinatorial regulations.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Cathepsin D: Regulation in mammary gland remodeling, misregulation in breast cancer.Cancer biology & therapy · 2010Article
- SPE-39 family proteins interact with the HOPS complex and function in lysosomal delivery.Molecular biology of the cell · 2009Article
- The BH3-only protein Bik/Blk/Nbk inhibits nuclear translocation of activated ERK1/2 to mediate IFNgamma-induced cell death.The Journal of cell biology · 2008Article
- Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways.Journal of molecular endocrinology · 2008Review
- E2-mediated cathepsin D (CTSD) activation involves looping of distal enhancer elements.Molecular oncology · 2008Article
- HMGN1 modulates estrogen-mediated transcriptional activation through interactions with specific DNA-binding transcription factors.Molecular and cellular biology · 2007Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cathepsin D (cath-D) gene, coding for a ubiquitous lysosomal aspartyl protease, is overexpressed in aggressive human breast cancers, and its transcription is induced by estrogens in hormone-responsive breast cancer cells. We have determined the structure and function of the proximal 5' upstream region of the human cath-D gene from MCF7 cells. We show that the promoter has a compound structure with features of both housekeeping genes (high G+C content and potential transcription factor Sp1 sites) and regulated genes (TATAA sequence). By RNase protection assay, we show that transcription is initiated at five major transcription sites (TSSI to -V) spanning 52 base pairs. In hormone-responsive breast cancer cells, estradiol increased by 6- to 10-fold the level of RNAs initiated at TSSI, which is located about 28 base pairs downstream from the TATA box. The specific regulation by estradiol of transcription starting at site I exclusively was confirmed by primer extension. Moreover, the same estradiol effect was observed in the ZR75-1 cell line and in MDA-MB231 estrogen-resistant breast cancer cells stably transfected with the estrogen receptor. Site-directed mutagenesis indicated that the TATA box is essential for initiation of cath-D gene transcription at TSSI. In breast cancer biopsy samples, high levels of TATA-dependent transcription were correlated with overexpression of cath-D mRNA. We conclude that cath-D behaves, depending on the conditions, as a housekeeping gene with multiple start sites or as a hormone-regulated gene that can be controlled from its TATA box.
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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.