科学家们发现，基因SOX2在肺部和食道鳞状细胞癌中被激活了，新成果发表在日前在《自然—遗传学》期刊上，揭示出干细胞与癌症的一种新关系。
鳞状细胞癌是出现在皮肤、口腔、食道、膀胱、前列腺和肺部等组织中的一种癌症。大约25%~30%的肺部癌症是鳞状细胞癌，并且与吸烟相关。在所有的食道癌症中，鳞状细胞癌的发生率只占10%，与吸烟、饮酒有关。
Matthew Meyerson和同事发现，基因SOX2在肺和食道的鳞状细胞癌中特别活跃。对食道和气管的发育来说，SOX2是一种重要基因，而且在重新程序化成熟细胞、使之成为干细胞的过程中，也发挥了重要作用。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Genetics 41, 1238 - 1242 (2009) 4 October 2009 | doi:10.1038/ng.465
SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas
Adam J Bass1,4,18, Hideo Watanabe1,3,4,18, Craig H Mermel1,3,4, Soyoung Yu1,3, Sven Perner5,6, Roel G Verhaak1,3,4, So Young Kim1,3, Leslie Wardwell1,3, Pablo Tamayo4, Irit Gat-Viks4, Alex H Ramos1,3,4, Michele S Woo1,3,4, Barbara A Weir1,3,4, Gad Getz4, Rameen Beroukhim1,4, Michael O'Kelly4, Amit Dutt1,3,4, Orit Rozenblatt-Rosen1,3, Piotr Dziunycz1, Justin Komisarof1, Lucian R Chirieac7, Christopher J LaFargue5, Veit Scheble6, Theresia Wilbertz6, Changqing Ma8, Shilpa Rao8, Hiroshi Nakagawa8,9, Douglas B Stairs8,9, Lin Lin10, Thomas J Giordano11, Patrick Wagner5, John D Minna12, Adi F Gazdar12, Chang Qi Zhu13, Marcia S Brose8,14, Ivan Cecconello15, Ulysses Ribeiro Jr15, Suely K Marie15, Olav Dahl16, Ramesh A Shivdasani1,2, Ming-Sound Tsao13, Mark A Rubin5, Kwok K Wong1,2, Aviv Regev4, William C Hahn1,4, David G Beer10, Anil K Rustgi8,9,17 & Matthew Meyerson1,3,4,7
Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development1, 2. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations3, is necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and cooperates in induction of pluripotent stem cells6, 7, 8. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.
1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
2 Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
3 Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
4 Broad Institute, Cambridge, Massachusetts, USA.
5 Department of Pathology, Weill Medical College of Cornell University, New York, New York, USA.
6 Institute of Pathology, Comprehensive Cancer Center, University Hospitals of Tuebingen, Tuebingen, Germany.
7 Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
8 Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
9 Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
10 Section of Thoracic Surgery, Department of Surgery, Ann Arbor, Michigan, USA.
11 Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
12 University of Texas Southwestern Medical Center, Dallas, Texas, USA.
13 University Health Network and Princess Margaret Hospital, Toronto, Canada.
14 Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
15 School of Medicine, University of S?o Paolo, S?o Paolo, Brazil.
16 Section of Oncology, University of Bergen, Bergen, Norway.
17 Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
18 These authors contributed equally to this work.
