{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T05:16:24Z","timestamp":1775279784400,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["19K16548"],"award-info":[{"award-number":["19K16548"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heterogeneous nuclear ribonucleoprotein K (hnRNPK) transcripts are abundant in estrogen receptor (ER)- or progesterone receptor (PR)-positive breast cancer. However, the biological functions of hnRNPK in the ER-mediated signaling pathway have remained largely unknown. Therefore, this study analyzes the functions of hnRNPK expression in the ER-mediated signaling pathway in breast cancer. We initially evaluated hnRNPK expression upon treatment with estradiol (E2) and ICI 182,780 in the ER\u03b1-positive breast carcinoma cell line MCF-7. The results revealed that E2 increased hnRNPK; however, hnRNPK expression was decreased with ICI 182,780 treatment, indicating estrogen dependency. We further evaluated the effects of hnRNPK knockdown in the ER-mediated signaling pathway in MCF-7 cells using small interfering RNAs. The results revealed that hnRNPK knockdown decreased ER\u03b1 expression and ER\u03b1 target gene pS2 by E2 treatment. As hnRNPK interacts with several other proteins, we explored the interaction between hnRNPK and ER\u03b1, which was demonstrated using immunoprecipitation and proximity ligation assay. Subsequently, we immunolocalized hnRNPK in patients with breast cancer, which revealed that hnRNPK immunoreactivity was significantly higher in ER\u03b1-positive carcinoma cells and significantly lower in Ki67-positive or proliferative carcinoma cells. These results indicated that hnRNPK directly interacted with ER\u03b1 and was involved in the ER-mediated signaling pathway in breast carcinoma. Furthermore, hnRNPK expression could be an additional target of endocrine therapy in patients with ER\u03b1-positive breast cancer.<\/jats:p>","DOI":"10.3390\/ijms22052581","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:39:07Z","timestamp":1614904747000},"page":"2581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Heterogeneous Nuclear Ribonucleoprotein K Is Involved in the Estrogen-Signaling Pathway in Breast Cancer"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-7500","authenticated-orcid":false,"given":"Erina","family":"Iwabuchi","sequence":"first","affiliation":[{"name":"Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3618-5652","authenticated-orcid":false,"given":"Yasuhiro","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDes), Tohoku University, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Department of Surgery, Tohoku Kosai Hospital, Sendai 980-0803, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironobu","family":"Sasano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/msb.2013.28","article-title":"Integrative genomics of gene and metabolic regulation by estrogen receptors \u03b1 and \u03b2, and their coregulators","volume":"9","author":"Charn","year":"2013","journal-title":"Mol. 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