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Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis

Renu Wadhwa1, Syuichi Takano, Kamaljit Kaur

  • 1Gene Function Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.

International Journal of Cancer
|January 21, 2006
PubMed

Insights

Mortalin, a protein that inactivates tumor suppressor p53, is elevated in human tumors. Increased mortalin expression promotes tumor growth and malignancy, suggesting it as a cancer therapy target.

Area of Science:

  • Molecular Biology
  • Oncology

Background:

  • Mortalin (mthsp70/GRP75/PBP74) interacts with and inactivates the tumor suppressor protein p53.
  • p53 plays a critical role in transcriptional activation and apoptosis, processes crucial for preventing cancer.

Purpose of the Study:

  • To investigate the role of mortalin expression in human tumorigenesis.
  • To determine if elevated mortalin contributes to cancer development and progression.

Main Methods:

  • Analysis of mortalin expression levels in various human tumor tissues and cell lines.
  • Immortalization of human embryonic fibroblasts using hTERT, with or without HPV E6/E7 genes.
  • Assessment of anchorage-independence and tumor formation in nude mice for subclones with altered mortalin expression.
  • Evaluation of mortalin's effect on breast carcinoma cell malignancy.

Main Results:

  • Mortalin expression was significantly elevated in numerous human tumors and all tested tumor-derived and immortalized cell lines.
  • Spontaneously increased mortalin levels in immortalized fibroblasts correlated with anchorage-independence and tumor formation in vivo.
  • Overexpression of mortalin enhanced the malignancy of breast carcinoma cells.

Conclusions:

  • Upregulation of mortalin is a significant contributor to tumorigenesis.
  • Mortalin represents a promising therapeutic target for cancer treatment.

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