| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Centre for Cutaneous Research, Barts & The London School of Medicine and Dentistry, Queen Mary, University of London, London E1 2AT, United Kingdom
Forkhead box (FOX) proteins have been shown to play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, longevity, and transformation. The functional importance of this gene family in normal human skin physiology and disease processes is not well understood. Activation of Sonic Hedgehog (Shh) signaling plays a key role in the development of basal cell carcinomas (BCCs) of the skin in humans. Recent studies have established that some FOX genes are downstream targets of Shh signaling. We have investigated the role of FOX proteins in transducing Shh effects in human skin by using degenerate PCR to identify FOX genes differentially expressed in BCCs. All three known FOXM1 isoforms (a, b, and c) were detected in human skin and cultured keratinocytes, and the transcriptionally active FOXM1b isoform was found to be up-regulated in BCCs. Real-time quantitative RT-PCR showed that the increase in FOXM1 mRNA levels was specific for BCCs and not a reflection of increased cell proliferation in that no up-regulation was seen in squamous cell carcinomas or proliferating primary human keratinocyte cultures. Immunostaining studies showed intense nuclear and cytoplasmic staining throughout BCC tumor islands and not confined to the periphery regions of the tumor where proliferating Ki-67-immunopositive cells are predominantly localized. Expression of the Shh target glioma transcription factor-1 (Gli1) in primary keratinocytes and other cell lines caused a significant elevation of FOXM1 mRNA level and transcriptional activity, indicating that FOXM1 is a downstream target of Gli1. Our data provide the first evidence that activation of Shh signaling via Gli1 is an important determinant of FOXM1 expression in mammalian cells. Given the role of FOXM1 in cell proliferation, the up-regulation of FOXM1 in BCCs may be one of the mechanisms whereby Shh signaling exerts its mitogenic effect on basal keratinocytes, leading to the development of this common human cancer.
This article has been cited by other articles:
|
|
 |
|
  M. Kasper, V. Jaks, M. Fiaschi, and R. Toftgard Hedgehog signalling in breast cancer Carcinogenesis, June 1, 2009; 30(6): 903 - 911. [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]
|
|
|
|
 |
|
 M. Yu, J. Gipp, J. W. Yoon, P. Iannaccone, D. Walterhouse, and W. Bushman Sonic Hedgehog-responsive Genes in the Fetal Prostate J. Biol. Chem., February 27, 2009; 284(9): 5620 - 5629. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. W. Neill, W. J. Harrison, M. S. Ikram, T. D.L. Williams, L. S. Bianchi, S. K. Nadendla, J. L. Green, L. Ghali, A.-M. Frischauf, E. A. O'Toole, et al. GLI1 repression of ERK activity correlates with colony formation and impaired migration in human epidermal keratinocytes Carcinogenesis, April 1, 2008; 29(4): 738 - 746. [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]
|
|
|
|
 |
|
 B. Stecca, C. Mas, V. Clement, M. Zbinden, R. Correa, V. Piguet, F. Beermann, and A. Ruiz i Altaba Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways PNAS, April 3, 2007; 104(14): 5895 - 5900. [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]
|
|
|
|
 |
|
 M.-T. Teh, D. Blaydon, L. R. Ghali, S. Edmunds, E. Pantazi, M. R. Barnes, I. M. Leigh, D. P. Kelsell, and M. P. Philpott Role for WNT16B in human epidermal keratinocyte proliferation and differentiation J. Cell Sci., January 15, 2007; 120(2): 330 - 339. [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]
|
|
|
|
 |
|
 N. Tsuda, S. Ishiyama, Y. Li, C. G. Ioannides, J. L. Abbruzzese, and D. Z. Chang Synthetic MicroRNA Designed to Target Glioma-Associated Antigen 1 Transcription Factor Inhibits Division and Induces Late Apoptosis in Pancreatic Tumor Cells. Clin. Cancer Res., November 1, 2006; 12(21): 6557 - 6564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takahashi, C. Furukawa, A. Takano, N. Ishikawa, T. Kato, S. Hayama, C. Suzuki, W. Yasui, K. Inai, S. Sone, et al. The Neuromedin U-Growth Hormone Secretagogue Receptor 1b/Neurotensin Receptor 1 Oncogenic Signaling Pathway as a Therapeutic Target for Lung Cancer Cancer Res., October 1, 2006; 66(19): 9408 - 9419. [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]
|
|
|
|
|
|
M. Kasper, H. Schnidar, G. W. Neill, M. Hanneder, S. Klingler, L. Blaas, C. Schmid, C. Hauser-Kronberger, G. Regl, M. P. Philpott, et al. Selective Modulation of Hedgehog/GLI Target Gene Expression by Epidermal Growth Factor Signaling in Human Keratinocytes. Mol. Cell. Biol., August 1, 2006; 26(16): 6283 - 6298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Liu, B. Dai, S.-H. Kang, K. Ban, F.-J. Huang, F. F. Lang, K. D. Aldape, T.-x. Xie, C. E. Pelloski, K. Xie, et al. FoxM1B Is Overexpressed in Human Glioblastomas and Critically Regulates the Tumorigenicity of Glioma Cells. Cancer Res., April 1, 2006; 66(7): 3593 - 3602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Adolphe, R. Hetherington, T. Ellis, and B. Wainwright Patched1 Functions as a Gatekeeper by Promoting Cell Cycle Progression Cancer Res., February 15, 2006; 66(4): 2081 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I.-M. Kim, T. Ackerson, S. Ramakrishna, M. Tretiakova, I-C. Wang, T. V. Kalin, M. L. Major, G. A. Gusarova, H. M. Yoder, R. H. Costa, et al. The Forkhead Box m1 Transcription Factor Stimulates the Proliferation of Tumor Cells during Development of Lung Cancer Cancer Res., February 15, 2006; 66(4): 2153 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. V. Kalin, I-C. Wang, T. J. Ackerson, M. L. Major, C. J. Detrisac, V. V. Kalinichenko, A. Lyubimov, and R. H. Costa Increased Levels of the FoxM1 Transcription Factor Accelerate Development and Progression of Prostate Carcinomas in both TRAMP and LADY Transgenic Mice Cancer Res., February 1, 2006; 66(3): 1712 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-T. Teh, D. Blaydon, T. Chaplin, N. J. Foot, S. Skoulakis, M. Raghavan, C. A. Harwood, C. M. Proby, M. P. Philpott, B. D. Young, et al. Genomewide Single Nucleotide Polymorphism Microarray Mapping in Basal Cell Carcinomas Unveils Uniparental Disomy as a Key Somatic Event Cancer Res., October 1, 2005; 65(19): 8597 - 8603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Wonsey and M. T. Follettie Loss of the Forkhead Transcription Factor FoxM1 Causes Centrosome Amplification and Mitotic Catastrophe Cancer Res., June 15, 2005; 65(12): 5181 - 5189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Y. M. Ma, T. H. K. Tong, A. M. S. Cheung, A. C. C. Tsang, W. Y. Leung, and K.-M. Yao Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c J. Cell Sci., February 15, 2005; 118(4): 795 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Pisarska, J. Bae, C. Klein, and A. J. W. Hsueh Forkhead L2 Is Expressed in the Ovary and Represses the Promoter Activity of the Steroidogenic Acute Regulatory Gene Endocrinology, July 1, 2004; 145(7): 3424 - 3433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. V. Kalinichenko, M. L. Major, X. Wang, V. Petrovic, J. Kuechle, H. M. Yoder, M. B. Dennewitz, B. Shin, A. Datta, P. Raychaudhuri, et al. Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor Genes & Dev., April 1, 2004; 18(7): 830 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. van den Boom, M. Wolter, R. Kuick, D. E. Misek, A. S. Youkilis, D. S. Wechsler, C. Sommer, G. Reifenberger, and S. M. Hanash Characterization of Gene Expression Profiles Associated with Glioma Progression Using Oligonucleotide-Based Microarray Analysis and Real-Time Reverse Transcription-Polymerase Chain Reaction Am. J. Pathol., September 1, 2003; 163(3): 1033 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, H. Kiyokawa, M. B. Dennewitz, and R. H. Costa The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration PNAS, December 24, 2002; 99(26): 16881 - 16886. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
