{"id":523555,"date":"2022-12-08T22:49:03","date_gmt":"2022-12-08T19:49:03","guid":{"rendered":"https:\/\/en.buradabiliyorum.com\/clues-found-regarding-tumor-suppressor-genes-breast-cancer-activity\/"},"modified":"2022-12-08T22:49:03","modified_gmt":"2022-12-08T19:49:03","slug":"clues-found-regarding-tumor-suppressor-genes-breast-cancer-activity","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/clues-found-regarding-tumor-suppressor-genes-breast-cancer-activity\/","title":{"rendered":"#Clues found regarding tumor suppressor gene&#8217;s breast cancer activity"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_88 counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of Contents<\/p>\n<label for=\"ez-toc-cssicon-toggle-item-6acd467978301\" class=\"ez-toc-cssicon-toggle-label\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #dd3333;color:#dd3333\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #dd3333;color:#dd3333\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/label><input type=\"checkbox\"  id=\"ez-toc-cssicon-toggle-item-6acd467978301\" checked aria-label=\"Toggle\" \/><nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-1'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/buradabiliyorum.com\/en\/clues-found-regarding-tumor-suppressor-genes-breast-cancer-activity\/#%E2%80%9CClues_found_regarding_tumor_suppressor_genes_breast_cancer_activity%E2%80%9D\" >&#8220;Clues found regarding tumor suppressor gene&#8217;s breast cancer activity&#8221;<\/a><\/li><\/ul><\/nav><\/div>\n<h1><span class=\"ez-toc-section\" id=\"%E2%80%9CClues_found_regarding_tumor_suppressor_genes_breast_cancer_activity%E2%80%9D\"><\/span>&#8220;Clues found regarding tumor suppressor gene&#8217;s breast cancer activity&#8221;<span class=\"ez-toc-section-end\"><\/span><\/h1>\n<div>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2022\/clues-found-regarding.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/2022\/clues-found-regarding.jpg\" data-sub-html=\"Credit: Saraswati Sukumar and Priya Pai\">\n<figure class=\"article-img\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/scx1.b-cdn.net\/csz\/news\/800a\/2022\/clues-found-regarding.jpg\" alt=\"Clues found regarding tumor suppressor gene's breast cancer activity\" title=\"Credit: Saraswati Sukumar and Priya Pai\" width=\"720\" height=\"405\"\/><figcaption class=\"text-darken text-low-up text-truncate-js text-truncate mt-3\">\n                Credit: Saraswati Sukumar and Priya Pai<br \/>\n            <\/figcaption><\/figure>\n<\/div>\n<\/div>\n<p>Researchers at the Johns Hopkins Kimmel Cancer Center have revealed how the gene HOXA5 may work to suppress formation of breast cancers. A new study indicates that it binds to another protein in an inflammatory cell pathway, boosting that protein&#8217;s cancer-suppressing properties.\n                                                <\/p>\n<p>                                                                                A de<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/download-scripts-themes-apps\/\" data-internallinksmanager029f6b8e52c=\"9\" title=\"Download Scripts &amp; Themes &amp; Apps\" target=\"_blank\" rel=\"noopener\">script<\/a>ion of the work was published in <i>Cancer Research<\/i>.<\/p>\n<p>HOXA5 is in cells lining the breast, where it normally acts as a tumor suppressor and transcription factor. It helps new cells mature toward performing their ultimate functions, says senior study author Saraswati Sukumar, Ph.D., a professor of oncology and pathology at the Johns Hopkins University School of Medicine who has been studying this protein for 25 years.<\/p>\n<p>Loss of HOXA5 results in cells becoming stuck in their incomplete differentiation stage, during which they begin to divide too much. This can lead to cancer. HOXA5 expression is lost in about 60% to 70% of all breast cancers, often occurring during an early stage of disease.  Loss of HOXA5 alone, however, is not always sufficient to start the breast cancer process, and Sukumar&#8217;s team focused on understanding other steps involved.<\/p>\n<p>In studies of breast cancer cell lines and in mice, Sukumar&#8217;s team discovered that HOXA5 has a partner\u2014it binds to and stabilizes the cellular protein I kappa B alpha (I\u03baB-\u03b1), which in turn inhibits NF-kappa B (NF-\u03baB), a protein complex. Typically, NF-\u03baB rushes to the nucleus and starts transcription of many cancer-causing genes, then I\u03baB-\u03b1 stops it. When HOXA5 is present, it&#8217;s able to help I\u03baB-\u03b1 suppress NF-\u03baB activity more potently, but when HOXA5 is lost, I\u03baB-\u03b1&#8217;s effect on NF-\u03baB is lessened, and the potential for cancer development is greater.<\/p>\n<p>&#8220;Our studies demonstrate that HOXA5 is acting to put brakes on a very important inflammatory pathway, which has been shown to be a promoter of the development of tumors,&#8221; Sukumar says. &#8220;Understanding precisely how this happens is of great importance, because increasing the amount of HOXA5 in these tumor cells may be a way forward to try to reverse the tumor formation process.&#8221;<\/p>\n<p>In laboratory studies, Priya Pai, lead author and postdoctoral fellow, studied a cell line from nonmalignant tissue lining the breast (epithelial cells) that contained mutations in key breast cancer genes. Breast cancer cells sometimes become resistant to endocrine treatment by acquiring mutations in the gene  PIK3CA, or resistant to anti-HER2 therapy through mutations in the HER2 gene. <\/p>\n<p>In cells that had mutations in the HER2 and PIK3CA genes, loss of HOXA5 induced the start of precancerous activity. When injected into mouse mammary ducts, the cells produced invasive tumor growth. The NF-\u03baB pathway was significantly upregulated in the cells after HOXA5 was silenced. As a result of activation of the NF-\u03baB pathway, multiple NF-\u03baB target genes involved in exacerbating cancerous changes, such as IL-6 and COX2, also were upregulated. <\/p>\n<p>Collectively, the data suggest that the presence of HOXA5 suppresses malignancy in breast epithelial cells by blunting NF-\u03baB action through stabilization of its inhibitor, I\u03baB-\u03b1.<\/p>\n<p>A new avenue of research is investigation of how lost HOXA5 can be replaced or reinstated so its tumor-suppressing functions can be restored to the cells, Sukumar says.<\/p>\n<div class=\"article-main__more p-4\">\n                                                                                                <strong>More information:<\/strong><br \/>\n                                                Priya Pai et al, HOXA5-<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/social-mediaa\/\" data-internallinksmanager029f6b8e52c=\"1\" title=\"Social Media\" target=\"_blank\" rel=\"noopener\">Media<\/a>ted Stabilization of I\u03baB\u03b1 Inhibits the NF-\u03baB Pathway and Suppresses Malignant Transformation of Breast Epithelial Cells, <i>Cancer Research<\/i> (2022).  <a rel=\"nofollow noopener\" target=\"_blank\" data-doi=\"1\" href=\"https:\/\/dx.doi.org\/10.1158\/0008-5472.CAN-21-4277\">DOI: 10.1158\/0008-5472.CAN-21-4277<\/a><\/p><\/div>\n<div class=\"d-inline-block text-medium my-4\">\n                                                Provided by<br \/>\n                                                                                                    Johns Hopkins University School of Medicine<br \/>\n                                                                                                        <a rel=\"nofollow noopener\" target=\"_blank\" class=\"icon_open\" href=\"http:\/\/www.hopkinsmedicine.org\/\"><br \/>\n                                                        <svg><use href=\"https:\/\/medx.b-cdn.net\/tmpl\/v6\/img\/svg\/sprite.svg#icon_open\" x=\"0\" y=\"0\"\/><\/svg><\/a><\/p><\/div>\n<p>                                        <!-- print only --><\/p>\n<div class=\"d-none d-print-block\">\n<p>\n                                                 <strong>Citation<\/strong>:<br \/>\n                                                 Clues found regarding tumor suppressor gene&#8217;s breast cancer activity (2022, December  8)<br \/>\n                                                 retrieved  8 December 2022<br \/>\n                                                 from https:\/\/medicalxpress.com\/<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/news\/\" data-internallinksmanager029f6b8e52c=\"2\" title=\"News\" target=\"_blank\" rel=\"noopener\">news<\/a>\/2022-12-clues-tumor-suppressor-gene-breast.html<\/p>\n<p>                                            This document is subject to copyright. 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A new study indicates that it binds to another protein in an inflammatory cell pathway, boosting that protein&#8217;s&#8230;<\/p>\n","protected":false},"author":1,"featured_media":523556,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"fifu_image_url":"https:\/\/scx2.b-cdn.net\/gfx\/news\/2022\/clues-found-regarding.jpg","fifu_image_alt":"","footnotes":""},"categories":[16],"tags":[],"class_list":["post-523555","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sciencee"],"_links":{"self":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/523555","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/comments?post=523555"}],"version-history":[{"count":0,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/523555\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media\/523556"}],"wp:attachment":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media?parent=523555"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/categories?post=523555"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/tags?post=523555"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}