ArticleThe Journal of clinical investigation2008
Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19Arf/p53 pathway lesions but not p16 Ink4a loss.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 63 citations in OpenAlex.
- Colitis-Associated Carcinoma: The Quintessential Epithelial Neoplasia Driven by Chronic Inflammation.Cells · 2026Review
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- Context-dependent effects of whole-genome duplication during mammary tumor recurrence.Scientific reports · 2021Article
- Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis.Biomolecules · 2021Review
- KIBRA Team Up with Partners to Promote Breast Cancer Metastasis.Pathology oncology research : POR · 2020Review
- A Multistage Murine Breast Cancer Model Reveals Long-Lived Premalignant Clones Refractory to Parity-Induced Protection.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- How to Choose a Mouse Model of Breast Cancer, a Genomic Perspective.Journal of mammary gland biology and neoplasia · 2019Review
- Potential protein markers for breast cancer recurrence: a retrospective cohort study.Cancer causes & control : CCC · 2019Article
- Notch3 inhibits epithelial-mesenchymal transition by activating Kibra-mediated Hippo/YAP signaling in breast cancer epithelial cells.Oncogenesis · 2016Article
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- Primary cilia modulate balance of canonical and non-canonical Wnt signaling responses in the injured kidney.Fibrogenesis & tissue repair · 2015Article
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- Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers.Nature · 2014Article
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- Epithelial-mesenchymal transition and tumor suppression are controlled by a reciprocal feedback loop between ZEB1 and Grainyhead-like-2.Cancer research · 2013Article
- Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis.Neuro-oncology · 2013Article
- Pathways to breast cancer recurrence.ISRN oncology · 2013Article
- Cervical cancers require the continuous expression of the human papillomavirus type 16 E7 oncoprotein even in the presence of the viral E6 oncoprotein.Cancer research · 2012Article
- Molecules involved in epithelial-mesenchymal transition and epithelial-stromal interaction in phyllodes tumors: implications for histologic grade and prognosis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Breast cancers frequently progress or relapse during targeted therapy, but the molecular mechanisms that enable escape remain poorly understood. We elucidated genetic determinants underlying tumor escape in a transgenic mouse model of Wnt pathway-driven breast cancer, wherein targeted therapy is simulated by abrogating doxycycline-dependent Wnt1 transgene expression within established tumors. In mice with intact tumor suppressor pathways, tumors typically circumvented doxycycline withdrawal by reactivating Wnt signaling, either via aberrant (doxycycline-independent) Wnt1 transgene expression or via acquired somatic mutations in the gene encoding beta-catenin. Germline introduction of mutant tumor suppressor alleles into the model altered the timing and mode of tumor escape. Relapses occurring in the context of null Ink4a/Arf alleles (disrupting both the p16 Ink4a and p19 Arf tumor suppressors) arose quickly and rarely reactivated the Wnt pathway. In addition, Ink4a/Arf-deficient relapses resembled p53-deficient relapses in that both displayed morphologic and molecular hallmarks of an epithelial-to-mesenchymal transition (EMT). Notably, Ink4a/Arf deficiency promoted relapse in the absence of gross genomic instability. Moreover, Ink4a/Arf-encoded proteins differed in their capacity to suppress oncogene independence. Isolated p19 Arf deficiency mirrored p53 deficiency in that both promoted rapid, EMT-associated mammary tumor escape, whereas isolated p16 Ink4a deficiency failed to accelerate relapse. Thus, p19 Arf/p53 pathway lesions may promote mammary cancer relapse even when inhibition of a targeted oncogenic signaling pathway remains in force.
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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.