ArticleThe American journal of pathology2009
Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Identification of a novel signature for prognostic stratification and integrative analyses in lung adenocarcinoma.Translational cancer research · 2026Article
- Anti-cancer potential of casein and its derivatives: novel strategies for cancer treatment.Medical oncology (Northwood, London, England) · 2024Review
- Role of Caveolae family-related proteins in the development of breast cancer.Frontiers in molecular biosciences · 2023Review
- Ten years of research on the role of BVES/ POPDC1 in human disease: a review.OncoTargets and therapy · 2019Review
- Breastfeeding and Immunohistochemical Expression of ki-67, p53 and BCL2 in Infiltrating Lobular Breast Carcinoma.PloS one · 2016Article
- The STAT5-regulated miR-193b locus restrains mammary stem and progenitor cell activity and alveolar differentiation.Developmental biology · 2014Article
- Mammary gland involution as an immunotherapeutic target for postpartum breast cancer.Journal of mammary gland biology and neoplasia · 2014Review
- Wounds that will not heal: pervasive cellular reprogramming in cancer.The American journal of pathology · 2013Review
- An ensemble prognostic model for colorectal cancer.PloS one · 2013Article
- The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis.Cell cycle (Georgetown, Tex.) · 2012Article
- Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells.Cancer biology & therapy · 2011Article
- Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment.Cell cycle (Georgetown, Tex.) · 2010Article
- Morphogenesis of the developing mammary gland: stage-dependent impact of adipocytes.Developmental biology · 2010Article
- Pregnancy and breast cancer: when they collide.Journal of mammary gland biology and neoplasia · 2009Review
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 3 countries.
Funding
Abstract
Here, we show that functional loss of a single gene is sufficient to confer constitutive milk protein production and protection against mammary tumor formation. Caveolin-3 (Cav-3), a muscle-specific caveolin-related gene, is highly expressed in muscle cells. We demonstrate that Cav-3 is also expressed in myoepithelial cells within the mammary gland. To determine whether genetic ablation of Cav-3 expression affects adult mammary gland development, we studied the phenotype(s) of Cav-3(-/-)-null mice. Interestingly, Cav-3(-/-) virgin mammary glands developed lobulo-alveolar hyperplasia, akin to the changes normally observed during pregnancy and lactation. Genome-wide expression profiling revealed up-regulation of gene transcripts associated with pregnancy/lactation, mammary stem cells, and human breast cancers, consistent with a constitutive lactogenic phenotype. Expression levels of three key transcriptional regulators of lactation, namely Elf5, Stat5a, and c-Myc, were also significantly elevated. Experiments with pregnant mice directly showed that Cav-3(-/-) mice underwent precocious lactation. Finally, using orthotopic tumor cell implantation, we demonstrated that virgin Cav-3(-/-) mice were dramatically protected against mammary tumor formation. Thus, Cav-3(-/-) mice are a novel preclinical model to study the protective effects of a lactogenic microenvironment on mammary tumor onset and progression. Our current studies have broad implications for using the lactogenic microenvironment as a paradigm to discover new therapies for the prevention and/or treatment of human breast cancers.
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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.