Title

Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis

College

College of Science

Department/Unit

Biology

Document Type

Article

Source Title

International Journal of Cancer

Volume

118

Issue

12

First Page

2973

Last Page

2980

Publication Date

2006

Abstract

Mortalin, also known as mthsp70/GRP75/PBP74, interacts with the tumor suppressor protein p53 and inactivates its transcriptional activation and apoptotic functions. Here, we examined the level of mortalin expression in a large variety of tumor tissues, tumor-derived and in vitro immortalized human cells. It was elevated in many human tumors, and in all of the tumor-derived and in vitro immortalized cells. In human embryonic fibroblasts immortalized with an expression plasmid for hTERT, the telomerase catalytic subunit, with or without human papillomavirus E6 and E7 genes, we found that subclones with spontaneously increased mortalin expression levels became anchorage-independent and acquired the ability to form tumors in nude mice. Furthermore, overexpression of mortalin was sufficient to increase the malignancy of breast carcinoma cells. The study demonstrates that upregulation of mortalin contributes significantly to tumorigenesis, and thus is a good candidate target for cancer therapy. © 2006 Wiley-Liss, Inc.

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Disciplines

Biochemistry, Biophysics, and Structural Biology

Keywords

Proteins; Tumors; Papillomaviruses; Metastasis; Chemotaxis; Nude mouse

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