{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nBPIFA4P, also known as BASE, was initially identified during a screen for novel transcripts enriched in breast and prostate cancer cells relative to essential normal tissues. In this study, a subtracted cDNA library from several breast cancer cell lines and a prostate cancer cell line revealed that BASE encodes a secreted protein that is expressed in many breast cancers while being absent from critical normal organs such as brain, liver, lung, kidney, and muscle. This cancer‐selective expression pattern suggests that BPIFA4P may serve as both a diagnostic marker and a potential therapeutic target in these cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "In further investigations using estrogen-responsive breast cancer cell models, BPIFA4P expression was shown to be modulated by hormonal signals. Specifically, estrogen was found to repress BPIFA4P transcription through an estrogen receptor alpha (ERα)–dependent mechanism. Promoter analyses identified a 2‐kb upstream enhancer with functional binding sites for both ERα and the transcription factor FoxA1, which emphasizes the gene’s complex, hormone-regulated expression and supports its role as a marker of estrogen-responsive tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "Additional studies on members of the PLUNC gene family, to which BPIFA4P is related, have demonstrated that genetic variants—such as single nucleotide polymorphisms in the promoter region—can influence gene activity and may contribute to cancer susceptibility. For example, a promoter SNP was associated with altered promoter activity in the PLUNC gene and linked to an increased risk for nasopharyngeal carcinoma. These findings broaden the functional significance of BPIFA4P, proposing a role not only in tumor detection and progression but also in mediating individual susceptibility to certain cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kristi A Egland, James J Vincent, Robert Strausberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0337425100"}], "href": "https://doi.org/10.1073/pnas.0337425100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12538848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12538848"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nancy Bretschneider, Heike Brand, Nicola Miller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen induces repression of the breast cancer and salivary gland expression gene in an estrogen receptor alpha-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-5647"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-5647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18172302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18172302"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Beina Liu, Rong Wang, Ying He "}, {"type": "b", "children": [{"type": "t", "text": "Functional Study of Polymorphism 1888 C>T in the Promoter Region of Human PLUNC Gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.amjms.2020.06.018"}], "href": "https://doi.org/10.1016/j.amjms.2020.06.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33722345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33722345"}]}]}]}