ArticleCancer research2009
hCLCA2 Is a p53-Inducible Inhibitor of Breast Cancer Cell Proliferation.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Functional Investigations of p53 Acetylation Enabled by Heterobifunctional Molecules.ACS chemical biology · 2024Article
- Multiomics2Targets identifies targets from cancer cohorts profiled with transcriptomics, proteomics, and phosphoproteomics.Cell reports methods · 2024Article
- TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.Journal of ovarian research · 2024Article
- CLCA2: A Potential Guardian against Premature Senescence and Skin Aging.Biomedicines · 2024Article
- Article
- FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.International journal of molecular sciences · 2023Review
- The role of human antigen R (HuR) in modulating proliferation, senescence and radiosensitivity of skin cells.Experimental and therapeutic medicine · 2022Article
- Chloride Channels and Transporters: Roles beyond Classical Cellular Homeostatic pH or Ion Balance in Cancers.Cancers · 2022Review
- Circulating Tumor Cells: Does Ion Transport Contribute to Intravascular Survival, Adhesion, Extravasation, and Metastatic Organotropism?Reviews of physiology, biochemistry and pharmacology · 2022Review
- Article
- The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-β/β-catenin signaling in HCC.International journal of biological sciences · 2022Article
- Article
- CLCA2 suppresses the proliferation, migration and invasion of cervical cancer.Experimental and therapeutic medicine · 2021Article
- The calcium-activated chloride channel-associated protein rCLCA2 is expressed throughout rat epidermis, facilitates apoptosis and is downmodulated by UVB.Histochemistry and cell biology · 2021Article
- Effects of the Tumor Environment on Ion Channels: Implication for Breast Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Epigenetic Repression of Chloride Channel Accessory 2 Transcription in Cardiac Fibroblast: Implication in Cardiac Fibrosis.Frontiers in cell and developmental biology · 2021Article
- Article
- The nuclear oncoprotein Fra-1: a transcription factor knocking on therapeutic applications' door.Oncogene · 2020Review
- CLCA2 expression is associated with survival among African American women with triple negative breast cancer.PloS one · 2020Article
- Prognostic value of chloride channel accessory mRNA expression in colon cancer.Oncology letters · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
hCLCA2 is frequently down-regulated in breast cancer and is a candidate tumor suppressor gene. We show here that the hCLCA2 gene is strongly induced by p53 in response to DNA damage. Adenoviral expression of p53 induces hCLCA2 in a variety of breast cell lines. Further, we find that p53 binds to consensus elements in the hCLCA2 promoter and mutation of these sites abolishes p53-responsiveness and induction by DNA damage. Adenoviral transduction of hCLCA2 into immortalized cells induces p53, CDK inhibitors p21 and p27, and cell cycle arrest by 24 hours, and caspase induction and apoptosis by 40 hours postinfection. Transduction of the malignant tumor cell line BT549 on the other hand does not induce p53, p21, or p27 but instead induces apoptosis directly and more rapidly. Knockout and knockdown studies indicate that growth inhibition and apoptosis are signaled via multiple pathways. Conversely, suppression of hCLCA2 by RNA interference enhances proliferation of MCF10A and reduces sensitivity to doxorubicin. Gene expression profiles indicate that hCLCA2 levels are strongly predictive of tumor cell sensitivity to doxorubicin and other chemotherapeutics. Because certain Cl(-) channels are proposed to promote apoptosis by reducing intracellular pH, we tested whether, and established that, hCLCA2 enhances Cl(-) current in breast cancer cells and reduces pH to approximately 6.7. These results reveal hCLCA2 as a novel p53-inducible growth inhibitor, explain how its down-regulation confers a survival advantage to tumor cells, and suggest both prognostic and therapeutic applications.
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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.