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Loss of metal transcription factor‐1 suppresses tumor growth through enhanced matrix deposition
Author(s) -
Haroon Zishan A.,
Amin Khalid,
Lichtlen Peter,
Sato Barbara,
Huynh Nhung T.,
Wang Zhaohui,
Schaffner Walter,
Murphy Brian J.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-1205com
Subject(s) - extracellular matrix , transcription factor , transforming growth factor , tissue transglutaminase , microbiology and biotechnology , chemistry , cancer research , biology , fibrosis , pathology , biochemistry , medicine , gene , enzyme
Metal transcription factor‐1 (MTF‐1) is a ubiquitous transcriptional regulator and chromatin in‐ sulator with roles in cellular stress responses and em‐ bryonic development. The studies described herein establish for the first time the involvement of MTF‐1 in tumor development. Genetically manipulated ras ‐trans‐ formed mouse embryonic fibroblasts (MEFs), wild‐type (MTF‐1 +/+ ), or nullizygous for MTF‐1 (MTF‐1 ‒/‒ ) were used to develop fibrosarcoma tumors. Loss of MTF‐1 resulted in delayed tumor growth associated with increased matrix collagen deposition and reduc‐ tions in vasculature density. Molecular consequences of MTF‐1 loss include increased expression and activation of the transforming growth factor–β1 (TGF‐β1) and tissue transglutaminase (tTG), two proteins with docu‐ mented roles in the production and stabilization of extracellular matrix (ECM). Our findings support the hypothesis that MTF‐1 enhances the ability of the developing tumor mass to evade fibrosis and scarring of the tumor, a critical step in tumor cell prolifera‐ tion.—Haroon, Z. A., Amin, K., Lichtlen, P., Sato, B., Huynh, N. T., Wang, Z., Schaffner, W., Murphy, B. J. Loss of metal transcription factor‐1 suppresses tumor growth through enhanced matrix deposition. FASEB J. 18, 1176 –1184 (2004)