ArticleOncogene2010
Genetic instability and mammary tumor formation in mice carrying mammary-specific disruption of Chk1 and p53.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 46 citations in OpenAlex.
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Case report: A germlineFrontiers in oncology · 2024Article
- CHK1-CDC25A-CDK1 regulate cell cycle progression and protect genome integrity in early mouse embryos.EMBO reports · 2023Article
- Checkpoint Kinase 1 Is a Key Signal Transducer of DNA Damage in the Early Mammalian Cleavage Embryo.International journal of molecular sciences · 2023Review
- Disrupted mitochondrial homeostasis coupled with mitotic arrest generates antineoplastic oxidative stress.Oncogene · 2022Article
- Checkpoint Responses to DNA Double-Strand Breaks.Annual review of biochemistry · 2020Review
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- Checkpoint Kinase 1 Expression Predicts Poor Prognosis in Nigerian Breast Cancer Patients.Molecular diagnosis & therapy · 2018Article
- Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma.BioMed research international · 2018Article
- Checkpoint kinase 1 is essential for normal B cell development and lymphomagenesis.Nature communications · 2017Article
- Cell cycle proteins as promising targets in cancer therapy.Nature reviews. Cancer · 2017Review
- Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.Oxidative medicine and cellular longevity · 2017Article
- Replication stress and cancer.Nature reviews. Cancer · 2015Review
- Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates.International journal of biological sciences · 2015Article
- Wnt-driven intestinal tumourigenesis is suppressed by Chk1 deficiency but enhanced by conditional haploinsufficiency.Oncogene · 2014Article
- Roles of Chk1 in cell biology and cancer therapy.International journal of cancer · 2014Review
- DNA damage response genes and the development of cancer metastasis.Radiation research · 2014Review
- Fos-dependent induction of Chk1 protects osteoblasts from replication stress.Cell cycle (Georgetown, Tex.) · 2014Article
- Is activation of the intra-S checkpoint in human fibroblasts an important factor in protection against UV-induced mutagenesis?Cell cycle (Georgetown, Tex.) · 2013Article
- Chk1 targeting reactivates PP2A tumor suppressor activity in cancer cells.Cancer research · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Checkpoint kinase 1 (Chk1) is a key element in the DNA-damage response pathway that is required for maintaining genomic stability. To study the potential role of Chk1 in mammary tumorigenesis, we disrupted it using a Cre/loxP system. We showed that although Chk1 heterozygosity caused abnormal development of the mammary gland, it was not sufficient to induce tumorigenesis. Simultaneous deletion of one copy of p53 failed to rescue the developmental defects; however, it synergistically induced mammary tumor formation in Chk1(+/-);MMTV-Cre animals with a median time to tumor latency of about 10 months. Chk1 deficiency caused a preponderance of abnormalities, including prolongation, multipolarity, misalignment, mitotic catastrophe and loss of spindle checkpoint, that are accompanied by reduced expression of several cell cycle regulators, including Mad2. On the other hand, we also showed that Chk1 deficiency inhibited mammary tumor formation in mice carrying a homozygous deletion of p53, uncovering a complex relationship between Chk1 and p53. Furthermore, inhibition of Chk1 with a specific inhibitor, SB-218078, or acute deletion of Chk1 using small hairpin RNA killed mammary tumor cells effectively. These data show that Chk1 is critical for maintaining genome integrity and serves as a double-edged sword for cancer: although its inhibition kills cancer cells, it also triggers tumorigenesis when favorable mutations are accumulated for cell growth.
Indexed as
Identifiers
What OpenQuestion holds
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.