Molecular regulation, membrane association and secretion of tumor cathepsin B

Upregulation, membrane association and secretion of cathepsin B have been shown to occur in many types of tumors and to correlate positively with their invasive and metastatic capabilities. To further understand changes in cathepsin B activity and localization, we have been examining its regulation...

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Published in:APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 1999-03, Vol.107 (1-6), p.28-37
Main Authors: FROSCH, BARBARA A., BERQUIN, ISABELLE, EMMERT-BUCK, MICHAEL R., MOIN, KAMIAR, SLOANE, BONNIE F.
Format: Article
Language:English
Subjects:
Animals
Cathepsin B
Cathepsin B - genetics
Cathepsin B - secretion
Cell Membrane - enzymology
cysteine protease
Humans
membrane protease
molecular regulation
Neoplasms - enzymology
Promoter Regions, Genetic
secretion
TATA Box
Transcription, Genetic
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Summary:Upregulation, membrane association and secretion of cathepsin B have been shown to occur in many types of tumors and to correlate positively with their invasive and metastatic capabilities. To further understand changes in cathepsin B activity and localization, we have been examining its regulation at many levels including transcription and trafficking. Our studies indicate that there may be three promoter regions in the cathepsin B gene. Of these, continued examination of the promoter upstream of exon I has indicated possible control by several regulatory factors including E‐box and Sp‐1 binding elements. Upregulation of cathepsin B at this level may account for some of the secretion of cathepsin B found in tumors. We have also gathered evidence that endo‐and exocytosis of cathepsin B may be regulated by ras and ras‐related proteins in addition to previously described trafficking systems. There is also evidence that several populations of lysosomes may exist and that trafficking to different populations may determine whether cathepsin B is secreted from the tumor cell or remains intracellular. Our results indicate that membrane association and secretion of cathepsin B is not a random process in the tumor cell, but rather part of a tightly controlled system.
ISSN:0903-4641
1600-0463
DOI:10.1111/j.1699-0463.1999.tb01523.x