This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, I.-M. Articles by Kalinichenko, V. V. Search for Related Content PubMed PubMed Citation Articles by Kim, I.-M. Articles by Kalinichenko, V. V.

The Forkhead Box m1 Transcription Factor Stimulates the Proliferation of Tumor Cells during Development of Lung Cancer

Departments of ¹ Medicine and ² Pathology, University of Chicago, Chicago, Illinois; and ³ Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois

Requests for reprints: Vladimir V. Kalinichenko, Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, Room W661, MC 6076, 5841 South Maryland Avenue, Chicago, IL 60637. Phone: 773-702-4024; Fax: 773-702-6500; E-mail: vkalin{at}medicine.bsd.uchicago.edu.

The proliferation-specific Forkhead Box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) regulates expression of cell cycle genes essential for progression into DNA replication and mitosis. Expression of Foxm1 is found in a variety of distinct human cancers including hepatocellular carcinomas, intrahepatic cholangiocarcinomas, basal cell carcinomas, ductal breast carcinomas, and anaplastic astrocytomas and glioblastomas. In this study, we show that human Foxm1 protein is abundantly expressed in highly proliferative human non–small cell lung cancers (NSCLC) as well as in mouse lung tumors induced by urethane. To determine the role of Foxm1 during the development of mouse lung tumors, we used IFN-inducible Mx-Cre recombinase transgene to delete mouse Foxm1 fl/fl–targeted allele before inducing lung tumors with urethane. We show that Mx-Cre Foxm1^–/– mice exhibit diminished proliferation of lung tumor cells causing a significant reduction in number and size of lung adenomas. Transient transfection experiments with A549 lung adenocarcinoma cells show that depletion of Foxm1 levels by short interfering RNA caused diminished DNA replication and mitosis and reduced anchorage-independent growth of cell colonies on soft agar. Foxm1-depleted A549 cells exhibit reduced expression of cell cycle–promoting cyclin A2 and cyclin B1 genes. These data show that Foxm1 stimulates the proliferation of tumor cells during progression of NSCLC. (Cancer Res 2006; 66(4): 2153-61)

This article has been cited by other articles:

				Y.-J. Chen, C. Dominguez-Brauer, Z. Wang, J. M. Asara, R. H. Costa, A. L. Tyner, L. F. Lau, and P. Raychaudhuri A Conserved Phosphorylation Site within the Forkhead Domain of FoxM1B Is Required for Its Activation by Cyclin-CDK1 J. Biol. Chem., October 30, 2009; 284(44): 30695 - 30707. [Abstract] [Full Text] [PDF]

				P.-J. Chua, G. W.-C. Yip, and B.-H. Bay Cell Cycle Arrest Induced by Hydrogen Peroxide Is Associated with Modulation of Oxidative Stress Related Genes in Breast Cancer Cells Experimental Biology and Medicine, September 1, 2009; 234(9): 1086 - 1094. [Abstract] [Full Text] [PDF]

				D F Calvisi, F Pinna, S Ladu, R Pellegrino, M M Simile, M Frau, M R De Miglio, M L Tomasi, V Sanna, M R Muroni, et al. Forkhead box M1B is a determinant of rat susceptibility to hepatocarcinogenesis and sustains ERK activity in human HCC Gut, May 1, 2009; 58(5): 679 - 687. [Abstract] [Full Text] [PDF]

				Q. Li, N. Zhang, Z. Jia, X. Le, B. Dai, D. Wei, S. Huang, D. Tan, and K. Xie Critical Role and Regulation of Transcription Factor FoxM1 in Human Gastric Cancer Angiogenesis and Progression Cancer Res., April 15, 2009; 69(8): 3501 - 3509. [Abstract] [Full Text] [PDF]

				U. B. McGovern, R. E. Francis, B. Peck, S. K. Guest, J. Wang, S. S. Myatt, J. Krol, J. M-M. Kwok, A. Polychronis, R. C. Coombes, et al. Gefitinib (Iressa) represses FOXM1 expression via FOXO3a in breast cancer Mol. Cancer Ther., March 1, 2009; 8(3): 582 - 591. [Abstract] [Full Text] [PDF]

				T. V. Kalin, I-C. Wang, L. Meliton, Y. Zhang, S. E. Wert, X. Ren, J. Snyder, S. M. Bell, L. Graf Jr., J. A. Whitsett, et al. Forkhead Box m1 transcription factor is required for perinatal lung function PNAS, December 9, 2008; 105(49): 19330 - 19335. [Abstract] [Full Text] [PDF]

				Y. Zhang, N. Zhang, B. Dai, M. Liu, R. Sawaya, K. Xie, and S. Huang FoxM1B Transcriptionally Regulates Vascular Endothelial Growth Factor Expression and Promotes the Angiogenesis and Growth of Glioma Cells Cancer Res., November 1, 2008; 68(21): 8733 - 8742. [Abstract] [Full Text] [PDF]

				T. V. Kalin, L. Meliton, A. Y. Meliton, X. Zhu, J. A. Whitsett, and V. V. Kalinichenko Pulmonary Mastocytosis and Enhanced Lung Inflammation in Mice Heterozygous Null for the Foxf1 Gene Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 390 - 399. [Abstract] [Full Text] [PDF]

				H. J. Park, R. H. Costa, L. F. Lau, A. L. Tyner, and P. Raychaudhuri Anaphase-Promoting Complex/Cyclosome-Cdh1-Mediated Proteolysis of the Forkhead Box M1 Transcription Factor Is Critical for Regulated Entry into S Phase Mol. Cell. Biol., September 1, 2008; 28(17): 5162 - 5171. [Abstract] [Full Text] [PDF]

				I-C. Wang, Y.-J. Chen, D. E. Hughes, T. Ackerson, M. L. Major, V. V. Kalinichenko, R. H. Costa, P. Raychaudhuri, A. L. Tyner, and L. F. Lau FoxM1 Regulates Transcription of JNK1 to Promote the G1/S Transition and Tumor Cell Invasiveness J. Biol. Chem., July 25, 2008; 283(30): 20770 - 20778. [Abstract] [Full Text] [PDF]

				J. M-M. Kwok, S. S. Myatt, C. M. Marson, R. C. Coombes, D. Constantinidou, and E. W-F. Lam Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression Mol. Cancer Ther., July 1, 2008; 7(7): 2022 - 2032. [Abstract] [Full Text] [PDF]

				S. K. M. Li, D. K. Smith, W. Y. Leung, A. M. S. Cheung, E. W. F. Lam, G. P. Dimri, and K.-M. Yao FoxM1c Counteracts Oxidative Stress-induced Senescence and Stimulates Bmi-1 Expression J. Biol. Chem., June 13, 2008; 283(24): 16545 - 16553. [Abstract] [Full Text] [PDF]

				V. Petrovic, R. H. Costa, L. F. Lau, P. Raychaudhuri, and A. L. Tyner FoxM1 Regulates Growth Factor-induced Expression of Kinase-interacting Stathmin (KIS) to Promote Cell Cycle Progression J. Biol. Chem., January 4, 2008; 283(1): 453 - 460. [Abstract] [Full Text] [PDF]

				U. Schuller, Q. Zhao, S. A. Godinho, V. M. Heine, R. H. Medema, D. Pellman, and D. H. Rowitch Forkhead Transcription Factor FoxM1 Regulates Mitotic Entry and Prevents Spindle Defects in Cerebellar Granule Neuron Precursors Mol. Cell. Biol., December 1, 2007; 27(23): 8259 - 8270. [Abstract] [Full Text] [PDF]

				Z. Wang, S. Banerjee, D. Kong, Y. Li, and F. H. Sarkar Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells Cancer Res., September 1, 2007; 67(17): 8293 - 8300. [Abstract] [Full Text] [PDF]

				I. Perez de Castro, G. de Carcer, and M. Malumbres A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy Carcinogenesis, May 1, 2007; 28(5): 899 - 912. [Abstract] [Full Text] [PDF]

				D. Malin, I.-M. Kim, E. Boetticher, T. V. Kalin, S. Ramakrishna, L. Meliton, V. Ustiyan, X. Zhu, and V. V. Kalinichenko Forkhead Box F1 Is Essential for Migration of Mesenchymal Cells and Directly Induces Integrin-Beta3 Expression Mol. Cell. Biol., April 1, 2007; 27(7): 2486 - 2498. [Abstract] [Full Text] [PDF]

				Y. Tan, P. Raychaudhuri, and R. H. Costa Chk2 Mediates Stabilization of the FoxM1 Transcription Factor To Stimulate Expression of DNA Repair Genes Mol. Cell. Biol., February 1, 2007; 27(3): 1007 - 1016. [Abstract] [Full Text] [PDF]

				Y. Maeda, V. Dave, and J. A. Whitsett Transcriptional Control of Lung Morphogenesis Physiol Rev, January 1, 2007; 87(1): 219 - 244. [Abstract] [Full Text] [PDF]

				S. K. Radhakrishnan, U. G. Bhat, D. E. Hughes, I-C. Wang, R. H. Costa, and A. L. Gartel Identification of a Chemical Inhibitor of the Oncogenic Transcription Factor Forkhead Box M1 Cancer Res., October 1, 2006; 66(19): 9731 - 9735. [Abstract] [Full Text] [PDF]

				P. A. Madureira, R. Varshochi, D. Constantinidou, R. E. Francis, R. C. Coombes, K.-M. Yao, and E. W.-F. Lam The Forkhead Box M1 Protein Regulates the Transcription of the Estrogen Receptor {alpha} in Breast Cancer Cells J. Biol. Chem., September 1, 2006; 281(35): 25167 - 25176. [Abstract] [Full Text] [PDF]

				T. Pramila, W. Wu, S. Miles, W. S. Noble, and L. L. Breeden The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle. Genes & Dev., August 15, 2006; 20(16): 2266 - 2278. [Abstract] [Full Text] [PDF]