{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:02:56Z","timestamp":1791270176897,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T00:00:00Z","timestamp":1337731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    MHC class I (MHC\u2010I) molecules are ubiquitously expressed on the cells of an organism. Study of the regulation of these molecules in normal and disease conditions is important. In tumour cells, the expression of MHC\u2010I molecules is very frequently lost, allowing these cells to evade the immune response. Cancers of different histology have shown total loss of MHC\u2010I molecule expression, due to a coordinated transcriptional down\u2010regulation of various antigen\u2010processing machinery (APM) components and\/or MHC\u2010I heavy chains. The mechanisms responsible for these alterations remain unclear. We determined the possible genes involved by comparing MHC\u2010I\u2010positive with MHC\u2010I\u2010negative murine metastases derived from the same fibrosarcoma tumour clone. MHC\u2010I\u2010negative metastases showed transcriptional down\u2010regulation of APM and MHC\u2010I heavy chains. The use of microarrays and subtraction cDNA libraries revealed four candidate genes responsible for this alteration, but two of them were ruled out by real\u2010time RT\u2010PCR analyses. The other two genes,\n                    <jats:italic>AP\u20102<\/jats:italic>\n                    \u03b1 and\n                    <jats:italic>Fhit<\/jats:italic>\n                    tumour suppressors, were studied by using siRNA to silence their expression in a MHC\u2010I\u2010positive metastatic cell line.\n                    <jats:italic>AP\u20102<\/jats:italic>\n                    \u03b1 inhibition did not modify transcriptional expression of APM components or MHC\u2010I heavy chains or surface expression of MHC\u2010I. In contrast, silencing of the\n                    <jats:italic>Fhit<\/jats:italic>\n                    gene produced the transcriptional down\u2010regulation of APM components and MHC\u2010I heavy chains and decreased MHC\u2010I surface expression. Moreover, transfection of\n                    <jats:italic>Fhit<\/jats:italic>\n                    in MHC\u2010I\u2010negative tumour cell lines restored MHC\u2010I cell surface expression. These data indicate that defects in\n                    <jats:italic>Fhit<\/jats:italic>\n                    expression may promote MHC\u2010I down\u2010regulation in cancer cells and allow escape from immunosurveillance\n                    <jats:sup>#<\/jats:sup>\n                    . Copyright \u00a9 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.4029","type":"journal-article","created":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T06:09:57Z","timestamp":1332828597000},"page":"367-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The tumour suppressor\n                    <i>Fhit<\/i>\n                    positively regulates MHC class I expression on cancer cells"],"prefix":"10.1002","volume":"227","author":[{"given":"Irene","family":"Romero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Collado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Algarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel M","family":"Garcia\u2010Lora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,23]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31405"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101324"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-007-0343-y"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104803"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203486"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090733"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-004-0560-6"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1516"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(01)83005-0"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(96)10075-X"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.2001.0404"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10290"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-004-0692-z"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3787"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.3.1462"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI498"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.1999.530607.x"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10906"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3734"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2368"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01547-07"},{"key":"e_1_2_7_23_2","first-page":"98","article-title":"Influence of class I H\u20102 gene expression on local tumor growth. 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