ArticleOncogene2000
Loss of p21WAF1/CIP1 accelerates Ras oncogenesis in a transgenic/knockout mammary cancer model.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 90 citations in OpenAlex.
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- Sustained ERK signaling promotes G2 cell cycle exit and primes cells for whole-genome duplication.Developmental cell · 2024Article
- Role of EGFR and FASN in breast cancer progression.Journal of cell communication and signaling · 2023Review
- Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells-Relevance for Understanding (Germ Cell) Tumorigenesis.International journal of molecular sciences · 2021Review
- TargetingCancers · 2021Review
- Functional Versatility of the CDK Inhibitor p57Frontiers in cell and developmental biology · 2020Review
- p21 in Cancer Research.Cancers · 2019Review
- RAS as Supporting Actor in Breast Cancer.Frontiers in oncology · 2019Review
- Article
- Cooperation Between Pten and Smad4 in Murine Salivary Gland Tumor Formation and Progression.Neoplasia (New York, N.Y.) · 2018Article
- Deconstructing networks of p53-mediated tumor suppression in vivo.Cell death and differentiation · 2018Review
- Genetically modified laboratory mice with sebaceous glands abnormalities.Cellular and molecular life sciences : CMLS · 2016Review
- Combined loss of PUMA and p21 accelerates c-MYC-driven lymphoma development considerably less than loss of one allele of p53.Oncogene · 2016Article
- Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma.OncoTargets and therapy · 2016Review
- Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma.The Journal of clinical investigation · 2015Article
- p53-mediated control of gene expression via mRNA translation during Endoplasmic Reticulum stress.Cell cycle (Georgetown, Tex.) · 2015Article
- Article
- Aberrant promoter hypermethylation of p21 (WAF1/CIP1) gene and its impact on expression and role of polymorphism in the risk of breast cancer.Molecular and cellular biochemistry · 2013Article
- Sumoylation is tumor-suppressive and confers proliferative quiescence to hematopoietic progenitors in Drosophila melanogaster larvae.Biology open · 2012Article
- Deconstructing p53 transcriptional networks in tumor suppression.Trends in cell biology · 2012Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Upregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and subsequent cell growth arrest or senescence is one mechanism by which normal cells are believed to respond to stress induced by the constitutively activated GTPase Ras. We hypothesize that in the absence of p21, the onset of Ras-dependent oncogenesis is accelerated. To test this hypothesis, we crossed MMTV/v-Ha-ras transgenic mice into a p21-deficient background. By 63 days of age, all 8 ras/p21-/- mice developed either malignant (mammary and/or salivary adenocarcinomas) or benign (Harderian hyperplasia) tumors. In contrast, by the same age, only one out of nine of the ras/p21+/+ mice developed a tumor. Furthermore, by 94 days of age, half of the ras/p21-/- mice, but none of the ras/p21+/+ mice, developed mammary tumors. p21-deficiency also accelerated the development of salivary (T50=66 days for ras/p21-/- vs T50=136 days for ras/p21+/+) and Harderian (T50=52 days for ras/p21-/- vs T50>221 days for ras/p21+/+) tumors. Furthermore, two out of the eight ras/p21-/- mice had metastatic lesions, one in its lungs, the other in its abdomen. None of the nine ras/p21+/+ mice had metastatic lesions. By 4 months of age, the mammary tumor multiplicity was 10-fold greater in ras/p21-/- (average 3.40 tumors/mouse) than in ras/p21+/+ (average 0.33 tumor/mouse) mice. However, once the tumors appeared, their growth rate, apoptosis level, and mitotic index were not affected by the loss of p21, suggesting that loss of p21 is critical in early but not late events of Ras oncogenesis. Altogether, the results show that tumor onset in MMTV/v-Ha-ras mice is p21-dependent with loss of p21 associated with earlier tumor appearance and increased tumor multiplicity and aggressiveness.
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