Cancer Research Landon Prizes for Basic and Translational Cancer Research Tumor Immunology: New Perspectives
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
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hoek, K.
Right arrow Articles by Halaban, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hoek, K.
Right arrow Articles by Halaban, R.
[Cancer Research 64, 5270-5282, August 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas

Keith Hoek1, David L. Rimm2, Kenneth R. Williams1, Hongyu Zhao3, Stephan Ariyan4, Aiping Lin1, Harriet M. Kluger5, Aaron J. Berger2, Elaine Cheng6, E. Sergio Trombetta7, Terence Wu1, Michio Niinobe8, Kazuaki Yoshikawa8, Gregory E. Hannigan9 and Ruth Halaban6

Departments of 1 Molecular Biophysics and Biochemistry, 2 Pathology, 3 Epidemiology, 4 Surgery, 5 Internal Medicine, 6 Dermatology, and 7 Cell Biology, Yale University School of Medicine, New Haven, Connecticut; 8 Division of Regulation of Macromolecular Functions, Institute for Protein Research, Osaka University, Osaka, Japan; and 9 Laboratory Medicine and Pathobiology, Cancer Research Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Affymetrix and spotted oligonucleotide microarrays were used to assess global differential gene expression comparing normal human melanocytes with six independent melanoma cell strains from advanced lesions. The data, validated at the protein level for selected genes, confirmed the overexpression in melanoma cells relative to normal melanocytes of several genes in the growth factor/receptor family that confer growth advantage and metastasis. In addition, novel pathways and patterns of associated expression in melanoma cells not reported before emerged, including the following: (a) activation of the NOTCH pathway; (b) increased Twist expression and altered expression of additional transcriptional regulators implicated in embryonic development and epidermal/mesenchymal transition; (c) coordinated activation of cancer/testis antigens; (d) coordinated down-regulation of several immune modulation genes, in particular in the IFN pathways; (e) down-regulation of several genes implicated in membrane trafficking events; and (f) down-regulation of growth suppressors, such as the Prader-Willi gene NECDIN, whose function was confirmed by overexpression of ectopic Flag-necdin. Validation of differential expression using melanoma tissue microarrays showed that reduced ubiquitin COOH-terminal esterase L1 in primary melanoma is associated with worse outcome and that increased expression of the basic helix-loop-helix protein Twist is associated with worse outcome. Some differentially expressed genes reside on chromosomal regions displaying common loss or gain in melanomas or are known to be regulated by CpG promoter methylation. These results provide a comprehensive view of changes in advanced melanoma relative to normal melanocytes and reveal new targets that can be used in assessing prognosis, staging, and therapy of melanoma patients.




This article has been cited by other articles:


Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
G. M. Kreizenbeck, A. J. Berger, A. Subtil, D. L. Rimm, and B. E. Gould Rothberg
Prognostic Significance of Cadherin-Based Adhesion Molecules in Cutaneous Malignant Melanoma
Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 949 - 958.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L.-M. Postovit, N. V. Margaryan, E. A. Seftor, D. A. Kirschmann, A. Lipavsky, W. W. Wheaton, D. E. Abbott, R. E. B. Seftor, and M. J. C. Hendrix
Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells
PNAS, March 18, 2008; 105(11): 4329 - 4334.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Abrahams, S. Mowla, M. I. Parker, C. R. Goding, and S. Prince
UV-mediated Regulation of the Anti-senescence Factor Tbx2
J. Biol. Chem., January 25, 2008; 283(4): 2223 - 2230.
[Abstract] [Full Text] [PDF]

Home page
 Am Soc Clin Oncol Ed BookHome page
T. F. Gajewski, E. A. Grimm, B. J. Nickoloff, and A. T. Weeraratna
New Potential Therapeutic Targets in Melanoma
ASCO Educational Book, January 1, 2008; 2008(1): 404 - 407.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
A. N. Shah, J. M. Summy, J. Zhang, S. I. Park, N. U. Parikh, and G. E. Gallick
Development and Characterization of Gemcitabine-Resistant Pancreatic Tumor Cells
Ann. Surg. Oncol., December 1, 2007; 14(12): 3629 - 3637.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
W. K. Kwok, M.-T. Ling, H. F. Yuen, Y.-C. Wong, and X. Wang
Role of p14ARF in TWIST-mediated senescence in prostate epithelial cells
Carcinogenesis, December 1, 2007; 28(12): 2467 - 2475.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Nambiar, A. Mirmohammadsadegh, M. Hassan, R. Mota, A. Marini, A. Alaoui, A. Tannapfel, J. H. Hegemann, and U. R. Hengge
Identification and functional characterization of ASK/Dbf4, a novel cell survival gene in cutaneous melanoma with prognostic relevance
Carcinogenesis, December 1, 2007; 28(12): 2501 - 2510.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H.-W. Lo, S.-C. Hsu, W. Xia, X. Cao, J.-Y. Shih, Y. Wei, J. L. Abbruzzese, G. N. Hortobagyi, and M.-C. Hung
Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-regulation of TWIST Gene Expression
Cancer Res., October 1, 2007; 67(19): 9066 - 9076.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. A. Watson, L. R. Ylagan, K. M. Trinkaus, W. E. Gillanders, M. J. Naughton, K. N. Weilbaecher, T. P. Fleming, and R. L. Aft
Isolation and Molecular Profiling of Bone Marrow Micrometastases Identifies TWIST1 as a Marker of Early Tumor Relapse in Breast Cancer Patients
Clin. Cancer Res., September 1, 2007; 13(17): 5001 - 5009.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
V. Bolos, J. Grego-Bessa, and J. L. de la Pompa
Notch Signaling in Development and Cancer
Endocr. Rev., May 1, 2007; 28(3): 339 - 363.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
H.-F. Yuen, Y.-P. Chan, M. Lok-Yee Wong, W.-K. Kwok, K.-K. Chan, P.-Y. Lee, G. Srivastava, S. Y.-K. Law, Y.-C. Wong, X. Wang, et al.
Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis
J. Clin. Pathol., May 1, 2007; 60(5): 510 - 514.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. R. Alonso, L. Tracey, P. Ortiz, B. Perez-Gomez, J. Palacios, M. Pollan, J. Linares, S. Serrano, A. I. Saez-Castillo, L. Sanchez, et al.
A High-Throughput Study in Melanoma Identifies Epithelial-Mesenchymal Transition as a Major Determinant of Metastasis
Cancer Res., April 1, 2007; 67(7): 3450 - 3460.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Z. Cheng, J. Chan, Q. Wang, W. Zhang, C. D. Sun, and L.-H. Wang
Twist Transcriptionally Up-regulates AKT2 in Breast Cancer Cells Leading to Increased Migration, Invasion, and Resistance to Paclitaxel
Cancer Res., March 1, 2007; 67(5): 1979 - 1987.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. M. Shields, N. E. Thomas, M. Cregger, A. J. Berger, M. Leslie, C. Torrice, H. Hao, S. Penland, J. Arbiser, G. Scott, et al.
Lack of Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Signaling Shows a New Type of Melanoma
Cancer Res., February 15, 2007; 67(4): 1502 - 1512.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
C. M. Ghajar, V. Suresh, S. R. Peyton, C. B. Raub, F. L. Meyskens Jr., S. C. George, and A. J. Putnam
A novel three-dimensional model to quantify metastatic melanoma invasion
Mol. Cancer Ther., February 1, 2007; 6(2): 552 - 561.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. Seliger, A. Fedorushchenko, W. Brenner, A. Ackermann, D. Atkins, S. Hanash, and R. Lichtenfels
Ubiquitin COOH-Terminal Hydrolase 1: A Biomarker of Renal Cell Carcinoma Associated with Enhanced Tumor Cell Proliferation and Migration[?Q1: Running head: UCHL1, a Biomarker of RCC. Short title OK?Q1]
Clin. Cancer Res., January 1, 2007; 13(1): 27 - 37.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. K. Lee, R. T.P. Poon, A. P. Yuen, M. T. Ling, W. K. Kwok, X. H. Wang, Y. C. Wong, X. Y. Guan, K. Man, K. L. Chau, et al.
Twist Overexpression Correlates with Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition.
Clin. Cancer Res., September 15, 2006; 12(18): 5369 - 5376.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
L. Packer, S. Pavey, A. Parker, M. Stark, P. Johansson, B. Clarke, P. Pollock, M. Ringner, and N. Hayward
Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN
Carcinogenesis, September 1, 2006; 27(9): 1778 - 1786.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L.-M. Postovit, E. A. Seftor, R. E.B. Seftor, and M. J.C. Hendrix
Influence of the Microenvironment on Melanoma Cell Fate Determination and Phenotype
Cancer Res., August 15, 2006; 66(16): 7833 - 7836.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. M. R. Bhat, N. Maddodi, C. Shashikant, and V. Setaluri
Transcriptional regulation of human MAP2 gene in melanoma: role of neuronal bHLH factors and Notch1 signaling
Nucleic Acids Res., August 11, 2006; 34(13): 3819 - 3832.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. J. Reu, S. I. Bae, L. Cherkassky, D. W. Leaman, D. Lindner, N. Beaulieu, A. R. MacLeod, and E. C. Borden
Overcoming Resistance to Interferon-Induced Apoptosis of Renal Carcinoma and Melanoma Cells by DNA Demethylation
J. Clin. Oncol., August 10, 2006; 24(23): 3771 - 3779.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
R Bauer, P J Wild, S Meyer, F Bataille, A Pauer, M Klinkhammer-Schalke, F Hofstaedter, and A K Bosserhoff
Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays
J. Clin. Pathol., July 1, 2006; 59(7): 699 - 705.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. M. McCarthy, K. A. DiVito, M. Sznol, D. Kovacs, R. Halaban, A. J. Berger, K. T. Flaherty, R. L. Camp, R. Lazova, D. L. Rimm, et al.
Expression of tumor necrosis factor-related apoptosis-inducing ligand receptors 1 and 2 in melanoma.
Clin. Cancer Res., June 15, 2006; 12(12): 3856 - 3863.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Yang, S. A. Mani, and R. A. Weinberg
Exploring a New Twist on Tumor Metastasis.
Cancer Res., May 1, 2006; 66(9): 4549 - 4552.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Z.-J. Liu, M. Xiao, K. Balint, K. S.M. Smalley, P. Brafford, R. Qiu, C. C. Pinnix, X. Li, and M. Herlyn
Notch1 Signaling Promotes Primary Melanoma Progression by Activating Mitogen-Activated Protein Kinase/Phosphatidylinositol 3-Kinase-Akt Pathways and Up-regulating N-Cadherin Expression.
Cancer Res., April 15, 2006; 66(8): 4182 - 4190.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
V. Winnepenninckx, V. Lazar, S. Michiels, P. Dessen, M. Stas, S. R. Alonso, M.-F. Avril, P. L. Ortiz Romero, T. Robert, O. Balacescu, et al.
Gene expression profiling of primary cutaneous melanoma and clinical outcome.
J Natl Cancer Inst, April 5, 2006; 98(7): 472 - 482.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. A. Seftor, K. M. Brown, L. Chin, D. A. Kirschmann, W. W. Wheaton, A. Protopopov, B. Feng, Y. Balagurunathan, J. M. Trent, B. J. Nickoloff, et al.
Epigenetic Transdifferentiation of Normal Melanocytes by a Metastatic Melanoma Microenvironment
Cancer Res., November 15, 2005; 65(22): 10164 - 10169.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. O. Gure, R. Chua, B. Williamson, M. Gonen, C. A. Ferrera, S. Gnjatic, G. Ritter, A. J.G. Simpson, Y.-T. Chen, L. J. Old, et al.
Cancer-Testis Genes Are Coordinately Expressed and Are Markers of Poor Outcome in Non-Small Cell Lung Cancer
Clin. Cancer Res., November 15, 2005; 11(22): 8055 - 8062.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Talantov, A. Mazumder, J. X. Yu, T. Briggs, Y. Jiang, J. Backus, D. Atkins, and Y. Wang
Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions
Clin. Cancer Res., October 15, 2005; 11(20): 7234 - 7242.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. K. Kwok, M.-T. Ling, T.-W. Lee, T. C.M. Lau, C. Zhou, X. Zhang, C. W. Chua, K. W. Chan, F. L. Chan, C. Glackin, et al.
Up-Regulation of TWIST in Prostate Cancer and Its Implication as a Therapeutic Target
Cancer Res., June 15, 2005; 65(12): 5153 - 5162.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. W. Vance, S. Carreira, G. Brosch, and C. R. Goding
Tbx2 Is Overexpressed and Plays an Important Role in Maintaining Proliferation and Suppression of Senescence in Melanomas
Cancer Res., March 15, 2005; 65(6): 2260 - 2268.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
V. von Felbert, F. Cordoba, J. Weissenberger, C. Vallan, M. Kato, I. Nakashima, L. R. Braathen, and J. Weis
Interleukin-6 Gene Ablation in a Transgenic Mouse Model of Malignant Skin Melanoma
Am. J. Pathol., March 1, 2005; 166(3): 831 - 841.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page

Vet. Pathol., November 1, 2004; 41(6): 712 - 712.
[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
Copyright © 2004 by the American Association for Cancer Research.