{"id":1245,"date":"2026-01-24T08:35:20","date_gmt":"2026-01-24T08:35:20","guid":{"rendered":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/hif-1-modulates-proliferation-and-differentiation-in-thyroid-carcinomas-via-pi3k-and-mapkerk-signall\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"hif-1-modulates-proliferation-and-differentiation-in-thyroid-carcinomas-via-pi3k-and-mapkerk-signall","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/hif-1-modulates-proliferation-and-differentiation-in-thyroid-carcinomas-via-pi3k-and-mapkerk-signall\/","title":{"rendered":"HIF-1? MODULATES PROLIFERATION AND DIFFERENTIATION IN THYROID CARCINOMAS VIA PI3K AND MAPK\/ERK SIGNALLING"},"content":{"rendered":"
Williams K.1<\/sup>, Cowen R.1<\/sup>, von Wasielewski R.2<\/sup>, Resch J.4<\/sup>, West C.3<\/sup>, Brabant G.4<\/sup><\/div>\n
1<\/sup>School of Pharmaccy, University of Manchester, UK, 2<\/sup>Dept. of Pathology, Medizinische Hochschule Hannover, Germany, 3<\/sup>Dept. Radiation Oncology, Manchester, UK, 4<\/sup>Dept. of Endocrinology, Christie Hospital, Manchester, UK<\/div>\n
\n

Abstract<\/h2>\n

HIF-1α upregulated in many tumour types appears to be critical for radio- and chemosensitivity in pre-clinical studies. As the regulation and function of HIF-1α is unknown in thyroid carcinomas, we evaluated basal expression and regulation of HIF-1α and target genes in primary thyroid carcinomas and in thyroid cancer cell lines (NPA, FTC-133, ARO).
We investigated HIF-1α and target genes (Glut-1, CA-IX) in snap-frozen tissue from primary thyroid carcinomas by IHC. Functional changes were studied for HIF-1α in all cell lines basally, under graded hypoxia (2%, 1%, anoxia, and the hypoxia mimetic CoCl2100 μM) with and without blockage of PI3K (Ly294002, 50 μM) and MAPK\/ERK (PD 98059, 50 μM) signaling. IF, western blot for HIF-α and the target genes Glut-1, CA-IX as well as a HIF-specific reporter gene assay were used as read-outs. HIF specific effects on proliferation were studied using the HIF antagonist YC-1. HIF-1α and target genes are expressed in dedifferentiated primary thyroid carcinomas and in NPA, FTC-133 and ARO cells. They are clearly up-regulated by hypoxia or CoCl2 stimulation. Using the PI3K inhibitor Ly294002 (FTC-133 cells) revealed that HIF-1α is stimulated by the PI3K pathway. Similarly, blockage of the MAPK\/ERK pathway by PD 98059 (NPA cells) had a strong inhibitory effect on HIF-1α expression and significantly reduced CA-IX protein levels. YC-1 (50 umol\/l) significantlt decreased proliferation in ARO and NPA cells.
Our data suggest that HIF-1α is expressed in primary thyroid carcinomas and appears upregulated in dedifferentiated tumours. HIF-1α is under oxygen control but is additionally regulated by the PI3K and the MAPK\/ERK pathway, central oncogenic pathways in the thyroid. These data may be of major clinical importance when considering the sensitizing role of HIF-1α inhibition in the modulation radiosensitivity in other epithelial type carcinomas<\/div>\n","protected":false},"excerpt":{"rendered":"

Williams K.1, Cowen R.1, von Wasielewski R.2, Resch J.4, West C.3, Brabant G.4 1School of Pharmaccy, University of Manchester, UK, 2Dept. of Pathology, Medizinische Hochschule Hannover, Germany, 3Dept. Radiation Oncology, Manchester, UK, 4Dept. of Endocrinology, Christie Hospital, Manchester, UK Abstract HIF-1α upregulated in many tumour types appears to be critical for radio- and chemosensitivity in Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[45,2,9],"tags":[],"class_list":["post-1245","post","type-post","status-publish","format-standard","hentry","category-volume-7-issue-3","category-journal-articles","category-volume-7"],"_links":{"self":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1245","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/comments?post=1245"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1245\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1245"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1245"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1245"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}