{"doi":"10.1016/j.stemcr.2020.12.012","title":"Depletion of Trp53 and Cdkn2a Does Not Promote Self-Renewal in the Mammary Gland but Amplifies Proliferation Induced by TNF-α","abstract":"The mammary epithelium undergoes several rounds of extensive proliferation during the female reproductive cycle. Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. Sufficient new cells have to be produced to maintain the integrity of a tissue, but excessive proliferation resulting in tumorigenesis needs to be prevented. Three well-known tumor suppressors, p53, p16INK4a, and p19ARF, have been connected to the limiting of stem cell self-renewal and proliferation. Here we investigate the roles of these three proteins in the regulation of self-renewal and proliferation of mammary epithelial cells. Using mammary epithelial-specific mouse models targeting Trp53 and Cdkn2a, the gene coding for p16INK4a and p19ARF, we demonstrate that p53, p16INK4a, and p19ARF do not play a significant role in the limitation of normal mammary epithelium self-renewal and proliferation, whereas in the presence of the inflammatory cytokine TNF-α, Trp53−/− Cdkn2a−/− mammary basal cells exhibit amplified proliferation.","journal":"Stem Cell Reports","year":2021,"id":196737,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":110559,"name":"Ferenc A. Scheeren","orcid":"0000-0002-8304-9023","position":1,"is_corresponding":false},{"id":110557,"name":"Shang Cai","orcid":"0000-0003-0630-7719","position":2,"is_corresponding":false},{"id":74032,"name":"Angera H. Kuo","orcid":"0000-0001-6955-9951","position":3,"is_corresponding":false},{"id":110561,"name":"Dalong Qian","orcid":"0000-0002-6261-5188","position":4,"is_corresponding":false},{"id":769485,"name":"William Hai Dang Ho","orcid":"0000-0003-1365-9624","position":5,"is_corresponding":false},{"id":55808,"name":"Michael F. Clarke","orcid":"0000-0001-6889-4926","position":6,"is_corresponding":false},{"id":769952,"name":"Linda J. van Weele","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:50:15.704473Z","pmid":"33482103","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}