Abstract
We sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC). A series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay. Out of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p = 0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p < 0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173, 55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased su...Continue Reading
References
Sep 1, 1994·Molecular and Cellular Biology·R J BohinskiJ A Whitsett
Aug 26, 1994·Cell·S L Ang, J Rossant
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·E LaiJ E Darnell
Jul 1, 1996·Molecular and Cellular Biology·K IkedaJ A Whitsett
Jul 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D J KwiatkowskiD J Sugarbaker
Jul 22, 1998·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M T StahlmanJ A Whitsett
Jun 19, 2004·Cancer Research·Balazs HalmosDaniel G Tenen
Sep 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Huajing WanJeffrey A Whitsett
Jan 26, 2005·The Journal of Biological Chemistry·Huajing WanJeffrey A Whitsett
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Mar 16, 2006·Journal of the National Cancer Institute·Yasuhiro TadaChristoph Plass
Jun 13, 2006·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Daniel B CostaBalazs Halmos
Jan 24, 2007·Physiological Reviews·Yutaka MaedaJeffrey A Whitsett
Jan 24, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Daniel B CostaBalazs Halmos
Nov 2, 2007·PLoS Medicine·Daniel B CostaSusumu Kobayashi
Nov 6, 2007·Nature·Barbara A WeirMatthew Meyerson
Dec 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tibor A RauchGerd P Pfeifer
Jan 24, 2008·Oncogene·K A KweiJ R Pollack
Jul 3, 2008·Cancer Research·Guosheng HuangBalazs Halmos
Dec 2, 2008·Journal of Cellular and Molecular Medicine·Justine A BarlettaLucian R Chirieac
Dec 17, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Steffen KoschmiederDaniel G Tenen
Oct 6, 2009·Nature Genetics·Adam J BassMatthew Meyerson
Jul 16, 2010·The American Journal of Surgical Pathology·Lynette M ShollJason L Hornick
Sep 8, 2010·Cell Research·Yunneng TangJianguo Song
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Apr 5, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Theresia WilbertzSven Perner
Citations
Feb 26, 2013·PloS One·Atsuyasu SatoMachiko Ikegami
Mar 31, 2015·Oncogene·W K C Cheung, D X Nguyen
Sep 3, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Yong-Qiang DongGui-Lin Yin
Jan 21, 2015·Developmental Biology·Vlasta LungovaSusan L Thibeault
Jul 29, 2016·Human Molecular Genetics·Rob HoutmeyersRuth M Arkell
May 26, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Audun BersaasSteen Mollerup
Oct 5, 2014·FEBS Letters·Joo-Hee AnKyung-Hee Choi
Mar 16, 2018·Genome Biology·Paulo P AmaralTony Kouzarides
Feb 20, 2018·Frontiers in Pharmacology·Lingling TangXiongbiao Wang
Mar 30, 2019·Genes & Development·Daniel T SwarrEdward E Morrisey
Sep 11, 2019·Cancer Medicine·Marco Antônio De Bastiani, Fábio Klamt
Jan 21, 2020·Oral Diseases·Yung-Ding BowRuei-Nian Li
Nov 16, 2017·Oncotarget·Tong-Hong WangChi-Yuan Chen
Feb 27, 2013·Oncology Reports·Jian-Wei LiangYu Zhang
Feb 7, 2019·American Journal of Respiratory Cell and Molecular Biology·Rachel Warren, Michael A O'Reilly
Apr 30, 2017·Clinical Epigenetics·J SongM N Hylkema
Aug 31, 2017·Clinical Epigenetics·Sipeng ShenDavid C Christiani
Nov 7, 2019·Frontiers in Oncology·Juan WangGang Ji
Aug 10, 2019·Cellular Oncology (Dordrecht)·Álvaro Quintanal-Villalonga, Sonia Molina-Pinelo
Sep 10, 2020·Cancers·Weilei HuYuan Wan