{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:31:27Z","timestamp":1792513887369,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,6,7]],"date-time":"2011-06-07T00:00:00Z","timestamp":1307404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The lactoferrin (<jats:italic>LTF<\/jats:italic>) gene, located at 3p21.3, behaves like a tumor suppressor gene in diverse tumors. To elucidate the exact role of <jats:italic>LTF<\/jats:italic> in NPC, we first detected its expression level in seven NPC cell lines by semi\u2010quantitative reverse transcription\u2010polymerase chain reaction (RT\u2010PCR). The results showed the mRNA level of <jats:italic>LTF<\/jats:italic> was nearly undetectable in all the seven NPC cell lines, while it could be detected in chronic nasopharyngitis tissues. Subsequently, we used methylation\u2010specific PCR (MSP), microsatellite assay, PCR\u2010single\u2010strand conformation polymorphism (PCR\u2010SSCP) and sequencing methods to examine the promoter methylation, loss of heterozygosity (LOH) and gene mutation of <jats:italic>LTF<\/jats:italic> in NPC cell lines respectively. Consequently, we found that 100% (7 of 7) of NPC cell lines were methylated in <jats:italic>LTF<\/jats:italic> promoter, only one cell line (14%, 1 of 7) had LOH and gene mutation of <jats:italic>LTF<\/jats:italic>, respectively, while <jats:italic>LTF<\/jats:italic> exhibited re\u2010expression in all cell lines after 5\u2010aza\u2010dC treatment, indicating promoter methylation should be the key mechanism causing <jats:italic>LTF<\/jats:italic> downregulation in NPC cell lines. Furthermore, patched methylation assay confirmed that promoter methylation could down\u2010regulate <jats:italic>LTF<\/jats:italic> gene expression in NPC cells. Finally, we investigated the function of <jats:italic>LTF<\/jats:italic> in NPC cell lines by gene transfection. Restoration of <jats:italic>LTF<\/jats:italic> expression in NPC cells resulted in blockage of cell cycle progression, significant inhibition of cell growth and a reduced colony\u2010formation capacity in vitro and obviously weaker tumor formation potential in vivo. In conclusion, our data indicate <jats:italic>LTF<\/jats:italic> may participate in NPC carcinogenesis as a negative effector, that is, a tumor suppressor gene. J. Cell. Biochem. 112: 1832\u20131843, 2011. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.23101","type":"journal-article","created":{"date-parts":[[2011,3,11]],"date-time":"2011-03-11T16:20:18Z","timestamp":1299860418000},"page":"1832-1843","source":"Crossref","is-referenced-by-count":31,"title":["Underlying mechanisms for LTF inactivation and its functional analysis in nasopharyngeal carcinoma cell 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