J Breast Cancer.  2011 Sep;14(3):167-174.

Heat Shock Protein as Molecular Targets for Breast Cancer Therapeutics

• Kim LS
• Kim JH

Abstract

Recent advances in the understanding of the molecular mechanisms involved in the breast cancer development and progression have led to the identification of numerous novel molecular targets. Among these, heat shock proteins (HSPs) are being emerging molecular target due to its diverse function in cancer cells. HSPs are highly conserved molecular chaperone that are synthesized by cell in response to various stress conditions. Mammalian HSPs have been classified into several families according to their molecular weight: HSP100, HSP90, HSP72, and small molecular HSPs (including HSP27). They are essential proteins that play a key role in cell survival through the cytoprotective mechanisms. In addition, HSPs are often overexpressed in a rage of cancers including breast cancer, and its overexpression seems to be associated with poor clinical outcomes. Also, HSP90 play a role in facilitating transformation by stabilizing the mutated and overexpressed oncoproteins found in breast cancer cell. Pharmacological targeting of HSP is therefore indicated and in the case of HSP90, numerous inhibitory drugs are undergoing clinical trial for treatment of breast cancer and other cancers. In this review, we describe the roles of HSPs in cancer cell and introduce the HSPs inhibitor as molecular target in cancer therapy and its recent clinical trials in breast cancer.

Keyword

Breast; Carcinoma; Chaperone; Heat; Shock

MeSH Terms

Breast
Breast Neoplasms
Cell Survival
Heat-Shock Proteins
Hot Temperature
Humans
Molecular Chaperones
Oncogene Proteins
Proteins
Rage
Shock
Heat-Shock Proteins
Molecular Chaperones
Oncogene Proteins
Proteins

Figure

• 

  Figure 1 HSP70/90 expression on breast cancer cell lines using Western blot assay. Expression of HSP70/90 are observated in both hormone receptor positive cell lines (1: MDA-MB 435; 2: MDA-MB 231) and hormone receptor negative cell lines (6: MCF-7; 7: T-47D). Also, MDA-MB 231LC3 (3), MDA-MB 231GFP (4), and MDA-MB 231BR3 cell line (5) expressed HSP70/90 proteins.

• 

  Figure 2 The effect of geldanamycin on breast cancer cell lines measured by MTT assay. Compared with DMSO and control group, gendanamycin markedly inhibited the cell growth in breast cancer cell lines in a dose-dependent manner.

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