Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M313178200 on January 14, 2004

J. Biol. Chem., Vol. 279, Issue 18, 18679-18687, April 30, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
279/18/18679    most recent
M313178200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Itano, N.
Right arrow Articles by Kimata, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Itano, N.
Right arrow Articles by Kimata, K.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Selective Expression and Functional Characteristics of Three Mammalian Hyaluronan Synthases in Oncogenic Malignant Transformation*

Naoki Itano{ddagger}§, Takahiro Sawai{ddagger}, Fukiko Atsumi||, Osamu Miyaishi**, Shun'ichiro Taniguchi{ddagger}{ddagger}, Reiji Kannagi§§§, Michinari Hamaguchi§¶¶, and Koji Kimata{ddagger}

From the {ddagger}Institute for Molecular Science of Medicine, Aichi Medical University, Nagakute, Aichi 480–1195, §Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, the ||Laboratory Animal Research Center and **Second Department of Pathology, Aichi Medical University, Nagakute, Aichi 480–1195, the {ddagger}{ddagger}Department of Molecular Oncology and Angiology, Angio-Aging Division, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, §§Program of Molecular Pathology, Aichi Cancer Center, Research Institute, Nagoya 464-8681, the ¶¶Department of Molecular Pathogenesis, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Japan

Malignant transformation of fibroblasts and epithelial cells is often accompanied by increased hyaluronan production and accumulation. Despite recent progress in the study of hyaluronan biosynthesis, the mechanisms underlying the transformation-induced overproduction of hyaluronan have not been elucidated. Here we report that activity and transcriptional levels of hyaluronan synthase (HAS) significantly increased after oncogenic malignant transformation of a rat 3Y1 fibroblast cell line. Of three HAS isoforms (HAS1, HAS2, and HAS3), only HAS2 gene expression was increased in the v-Ha-ras transformed 3Y1 cells, which show less malignancy. In contrast, both HAS1 and HAS2 expressions were elevated in the highly malignant cells transformed with v-src and/or v-fos. To assess the contribution of HAS expression to the oncogenic malignant transformation, we established stable cell transfectants expressing sense and antisense HAS genes. Antisense suppression of the HAS2 expression significantly decreased hyaluronan production in the cells transformed by the oncogenic v-Ha-ras and eventually led to a reduction in tumorigenicity in the rat peritoneum. The introduction of the HAS1 and HAS2 genes promoted the growth of subcutaneous tumors in a manner dependent on the levels of hyaluronan synthesis. Significant growth promotion was observed within a wide range of HAS1 expression. In contrast, the growth stimulation was only seen within a narrow range of HAS2 expression, and high levels of HAS2 expression even inhibited tumor growth. These results suggest that proper regulation of the expression of each HAS isoform is required for optimal malignant transformation and tumor growth.


Received for publication, December 3, 2003 , and in revised form, January 9, 2004.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AB097568 and AB097569.

* This study was supported by grants from the Core Research for Evolutional Science and Technology of the Japan Science and Technology Corporation, the preparatory grant for the research at the Division of Matrix Glycoconjugates, Research Center for Infectious Disease, Aichi Medical University, grants-in-aid for Young Scientists (B) and grants-in-aid for Scientific Research on Priority Areas from the Japan's Ministry of Education, Culture, Sports, Science and Technology, the Aichi Cancer Research Foundation, and special research funds from Seikagaku Corporation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 81-52-264-4811 (ext. 2095); Fax: 81-561-63-3532; E-mail: itano{at}amugw.aichi-med-u.ac.jp.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
A. Ghosh, H. Kuppusamy, and L. M. Pilarski
Aberrant Splice Variants of HAS1 (Hyaluronan Synthase 1) Multimerize with and Modulate Normally Spliced HAS1 Protein: A POTENTIAL MECHANISM PROMOTING HUMAN CANCER
J. Biol. Chem., July 10, 2009; 284(28): 18840 - 18850.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
A. G. Bharadwaj, J. L. Kovar, E. Loughman, C. Elowsky, G. G. Oakley, and M. A. Simpson
Spontaneous Metastasis of Prostate Cancer Is Promoted by Excess Hyaluronan Synthesis and Processing
Am. J. Pathol., March 1, 2009; 174(3): 1027 - 1036.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Adamia, A. A. Reichert, H. Kuppusamy, J. Kriangkum, A. Ghosh, J. J. Hodges, P. M. Pilarski, S. P. Treon, M. J. Mant, T. Reiman, et al.
Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia
Blood, December 15, 2008; 112(13): 5111 - 5121.
[Abstract] [Full Text] [PDF]


Home page
J. Histochem. Cytochem.Home page
K. Rilla, R. Tiihonen, A. Kultti, M. Tammi, and R. Tammi
Pericellular Hyaluronan Coat Visualized in Live Cells With a Fluorescent Probe Is Scaffolded by Plasma Membrane Protrusions
J. Histochem. Cytochem., October 1, 2008; 56(10): 901 - 910.
[Abstract] [Full Text] [PDF]


Home page
J BiochemHome page
N. Itano
Simple Primary Structure, Complex Turnover Regulation and Multiple Roles of Hyaluronan
J. Biochem., August 1, 2008; 144(2): 131 - 137.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
S. Misra, L. M. Obeid, Y. A. Hannun, S. Minamisawa, F. G. Berger, R. R. Markwald, B. P. Toole, and S. Ghatak
Hyaluronan Constitutively Regulates Activation of COX-2-mediated Cell Survival Activity in Intestinal Epithelial and Colon Carcinoma Cells
J. Biol. Chem., May 23, 2008; 283(21): 14335 - 14344.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
R. Golshani, L. Lopez, V. Estrella, M. Kramer, N. Iida, and V. B. Lokeshwar
Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44
Cancer Res., January 15, 2008; 68(2): 483 - 491.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
H. Koyama, N. Kobayashi, M. Harada, M. Takeoka, Y. Kawai, K. Sano, M. Fujimori, J. Amano, T. Ohhashi, R. Kannagi, et al.
Significance of Tumor-Associated Stroma in Promotion of Intratumoral Lymphangiogenesis: Pivotal Role of a Hyaluronan-Rich Tumor Microenvironment
Am. J. Pathol., January 1, 2008; 172(1): 179 - 193.
[Abstract] [Full Text] [PDF]


Home page
Stem CellsHome page
M. Choudhary, X. Zhang, P. Stojkovic, L. Hyslop, G. Anyfantis, M. Herbert, A. P. Murdoch, M. Stojkovic, and M. Lako
Putative Role of Hyaluronan and Its Related Genes, HAS2 and RHAMM, in Human Early Preimplantation Embryogenesis and Embryonic Stem Cell Characterization
Stem Cells, December 1, 2007; 25(12): 3045 - 3057.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
A. G. Bharadwaj, K. Rector, and M. A. Simpson
Inducible Hyaluronan Production Reveals Differential Effects on Prostate Tumor Cell Growth and Tumor Angiogenesis
J. Biol. Chem., July 13, 2007; 282(28): 20561 - 20572.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
H. Koyama, T. Hibi, Z. Isogai, M. Yoneda, M. Fujimori, J. Amano, M. Kawakubo, R. Kannagi, K. Kimata, S. Taniguchi, et al.
Hyperproduction of Hyaluronan in Neu-Induced Mammary Tumor Accelerates Angiogenesis through Stromal Cell Recruitment: Possible Involvement of Versican/PG-M
Am. J. Pathol., March 1, 2007; 170(3): 1086 - 1099.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
S. Misra, B. P. Toole, and S. Ghatak
Hyaluronan Constitutively Regulates Activation of Multiple Receptor Tyrosine Kinases in Epithelial and Carcinoma Cells
J. Biol. Chem., November 17, 2006; 281(46): 34936 - 34941.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
G. W. Yip, M. Smollich, and M. Gotte
Therapeutic value of glycosaminoglycans in cancer.
Mol. Cancer Ther., September 1, 2006; 5(9): 2139 - 2148.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
M. A. Simpson
Concurrent Expression of Hyaluronan Biosynthetic and Processing Enzymes Promotes Growth and Vascularization of Prostate Tumors in Mice
Am. J. Pathol., July 1, 2006; 169(1): 247 - 257.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. I. Lopez, T. D. Camenisch, M. V. Stevens, B. J. Sands, J. McDonald, and J. A. Schroeder
CD44 Attenuates Metastatic Invasion during Breast Cancer Progression
Cancer Res., August 1, 2005; 65(15): 6755 - 6763.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
L. Udabage, G. R. Brownlee, M. Waltham, T. Blick, E. C. Walker, P. Heldin, S. K. Nilsson, E. W. Thompson, and T. J. Brown
Antisense-Mediated Suppression of Hyaluronan Synthase 2 Inhibits the Tumorigenesis and Progression of Breast Cancer
Cancer Res., July 15, 2005; 65(14): 6139 - 6150.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Adamia, T. Reiman, M. Crainie, M. J. Mant, A. R. Belch, and L. M. Pilarski
Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant indicator of poor outcome in multiple myeloma
Blood, June 15, 2005; 105(12): 4836 - 4844.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
S. Misra, S. Ghatak, and B. P. Toole
Regulation of MDR1 Expression and Drug Resistance by a Positive Feedback Loop Involving Hyaluronan, Phosphoinositide 3-Kinase, and ErbB2
J. Biol. Chem., May 27, 2005; 280(21): 20310 - 20315.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
I. Kakizaki, K. Kojima, K. Takagaki, M. Endo, R. Kannagi, M. Ito, Y. Maruo, H. Sato, T. Yasuda, S. Mita, et al.
A Novel Mechanism for the Inhibition of Hyaluronan Biosynthesis by 4-Methylumbelliferone
J. Biol. Chem., August 6, 2004; 279(32): 33281 - 33289.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement