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Type I IFN stimulates IFI16-mediated aromatase expression in adipocytes that promotes E-2-dependent growth of ER-positive breast cancer
DC Field | Value | Language |
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dc.contributor.author | Ka, Na-Lee | - |
dc.contributor.author | Lim, Ga Young | - |
dc.contributor.author | Kim, Seung-Su | - |
dc.contributor.author | Hwang, Sewon | - |
dc.contributor.author | Han, Juhyeong | - |
dc.contributor.author | Lee, Yun-Hee | - |
dc.contributor.author | Lee, Mi-Ock | - |
dc.date.accessioned | 2022-06-21T08:31:38Z | - |
dc.date.available | 2022-06-21T08:31:38Z | - |
dc.date.created | 2022-05-31 | - |
dc.date.issued | 2022-06 | - |
dc.identifier.citation | Cellular and Molecular Life Sciences, Vol.79 No.6, p. 306 | - |
dc.identifier.issn | 1420-682X | - |
dc.identifier.uri | https://hdl.handle.net/10371/182694 | - |
dc.description.abstract | Although type I interferons (IFNs) play multifaceted roles during tumorigenesis and cancer treatment, the interplay between type I IFNs and estrogen signaling in breast cancer (BC) microenvironment is not well understood. Here, we report a novel function of type I IFNs in inducing aromatase expression in adipose tissues surrounding BC, which potentiates the E-2-dependent growth of estrogen receptor (ER)-positive BC. First, we found that expression levels of type I IFNs correlate negatively with clinical outcome but positively with tumor grade in patients with ER-positive BC. Levels of type I IFNs were elevated in cocultured media of immune cells and BC cells, which increased aromatase expression and E-2 production in Simpson-Golabi-Behmel syndrome preadipocytes. The type I IFN-induced aromatase expression was dependent on IFN-gamma-inducible protein 16 (IFI16), which is encoded by an interferon-stimulated gene. At the molecular level, type I IFNs led to recruitment of HIF1 alpha-IFI16-PRMT2 complex to the hypoxia-response element located in the aromatase PI.3/PII promoter. Next, we generated an adipocyte-specific Ifi204, which is a mouse ortholog of human IFI16, knockout mouse (Ifi204-AKO). IFN beta induced E-2 production in the preadipocytes isolated from the control mice, but such E-2 production was far lower in the Ifi204-AKO preadipocytes. Importantly, the growth of orthotopically inoculated E0771 ER-positive mammary tumors was reduced significantly in the Ifi204-AKO mice. Taken together, our findings provide novel insights into the crosstalk between type I IFNs and estrogen signaling in the progression of ER-positive BC. | - |
dc.language | 영어 | - |
dc.publisher | Birkhauser Verlag | - |
dc.title | Type I IFN stimulates IFI16-mediated aromatase expression in adipocytes that promotes E-2-dependent growth of ER-positive breast cancer | - |
dc.type | Article | - |
dc.identifier.doi | 10.1007/s00018-022-04333-y | - |
dc.citation.journaltitle | Cellular and Molecular Life Sciences | - |
dc.identifier.wosid | 000798340300001 | - |
dc.citation.number | 6 | - |
dc.citation.startpage | 306 | - |
dc.citation.volume | 79 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Lee, Yun-Hee | - |
dc.contributor.affiliatedAuthor | Lee, Mi-Ock | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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