ArticleProceedings of the National Academy of Sciences of the United States of America2010
Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Models for Studying Ductal Carcinoma In Situ Progression.Advances in experimental medicine and biology · 2025Review
- Advances in Immunocompetent Mouse and Rat Models.Cold Spring Harbor perspectives in medicine · 2024Review
- Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells.Cell biology and toxicology · 2023Article
- In Vivo Gene Delivery into Mouse Mammary Epithelial Cells Through Mammary Intraductal Injection.Journal of visualized experiments : JoVE · 2023Article
- miR-135a-5p overexpression in peripheral blood-derived exosomes mediates vascular injury in type 2 diabetes patients.Frontiers in endocrinology · 2023Article
- Interaction between HER2 and ATM predicts poor survival in bladder cancer patients.Journal of cellular and molecular medicine · 2022Article
- Targeting the Pro-survival Protein BCL-2 to Prevent Breast Cancer.Cancer prevention research (Philadelphia, Pa.) · 2022Article
- Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma.Cancers · 2021Article
- Intraductal Injection of Lentivirus Vectors for Stably Introducing Genes into Rat Mammary Epithelial Cells in Vivo.Journal of mammary gland biology and neoplasia · 2020Article
- Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions.Breast cancer research : BCR · 2018Article
- WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation.Cell research · 2017Article
- Article
- Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress.Oncogene · 2016Article
- APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication.Cell reports · 2016Article
- Review
- Effective intra-S checkpoint responses to UVC in primary human melanocytes and melanoma cell lines.Pigment cell & melanoma research · 2016Article
- A Novel Aspect of Tumorigenesis-BMI1 Functions in Regulating DNA Damage Response.Biomolecules · 2015Review
- Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence.Breast cancer research : BCR · 2015Article
- A p53/ARF-dependent anticancer barrier activates senescence and blocks tumorigenesis without impacting apoptosis.Molecular cancer research : MCR · 2015Article
- Krt6a-positive mammary epithelial progenitors are not at increased vulnerability to tumorigenesis initiated by ErbB2.PloS one · 2015Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.
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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.