{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T03:33:57Z","timestamp":1767065637892},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,7,3]],"date-time":"2011-07-03T00:00:00Z","timestamp":1309651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p>Recent studies have shown that intratumoral cholestasis is a hallmark of <jats:italic>CTNNB1<\/jats:italic> mutations in hepatocellular carcinomas (HCC). Here, we analyzed the expressions of genes involved in bile acid and bilirubin metabolism and their correlation with the mutational status of <jats:italic>CTNNB1<\/jats:italic> in a series of HCC. The expressions of <jats:italic>CYP7A1<\/jats:italic> and <jats:italic>CYP27A1<\/jats:italic>, which encode rate\u2010limiting enzymes in bile acid synthesis, were unaltered or only marginally increased in <jats:italic>CTNNB1<\/jats:italic>\u2010mutated HCC compared with those in HCC with wild\u2010type <jats:italic>CTNNB1<\/jats:italic>. Among the genes involved in bile acid and bilirubin transport, the expression of <jats:italic>SLCO1B3<\/jats:italic> was significantly elevated in HCC with <jats:italic>CTNNB1<\/jats:italic> mutations, whereas the expression of <jats:italic>ABCC4<\/jats:italic> was elevated in HCC with wild\u2010type <jats:italic>CTNNB1<\/jats:italic>. Immunohistochemistry confirmed the frequent expression of SLCO1B3 in <jats:italic>CTNNB1<\/jats:italic>\u2010mutated HCC at the protein level, but not in most HCC with wild\u2010type <jats:italic>CTNNB1<\/jats:italic>. Immunohistochemistry for MRP4 (encoded by <jats:italic>ABCC4<\/jats:italic>) partly agreed with <jats:italic>ABCC4<\/jats:italic> expression, but most cases did not express detectable levels of MRP4. Notably, all HCC with bile accumulation, including those without <jats:italic>CTNNB1<\/jats:italic> mutations, expressed SLCO1B3, suggesting that SLCO1B3 expression, rather than <jats:italic>CTNNB1<\/jats:italic> mutation, is the critical determinant of intratumoral cholestasis. As SLCO1B3 is involved in the uptake of a number of chemotherapeutic and diagnostic agents, SLCO1B3 expression and the status of <jats:italic>CTNNB1<\/jats:italic> mutation might need to be considered in the drug delivery to HCC. (<jats:italic>Cancer Sci<\/jats:italic> 2011; 102: 1742\u20131747)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2011.01990.x","type":"journal-article","created":{"date-parts":[[2011,5,25]],"date-time":"2011-05-25T16:49:15Z","timestamp":1306342155000},"page":"1742-1747","source":"Crossref","is-referenced-by-count":37,"title":["Expression of SLCO1B3 is associated with intratumoral cholestasis and <i>CTNNB1<\/i> mutations in hepatocellular carcinoma"],"prefix":"10.1111","volume":"102","author":[{"given":"Shigeki","family":"Sekine","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiko","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Ojima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yae","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,7,3]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-7568-6"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161712"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2619"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1121435"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1078"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl249"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2169"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03798.x"},{"key":"e_1_2_7_10_2","first-page":"2524","article-title":"Activation 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