AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer

Jose V Moyano ¹, Joseph R Evans , Feng Chen

⁰Cell Death Regulation Laboratory, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

The Journal of Clinical Investigation +

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January 6, 2006

View abstract on PubMed

Summary

Alpha-basic-crystallin (alphaB-crystallin) is a novel oncoprotein driving aggressive basal-like breast cancer. Its presence predicts poor survival, and targeting the MEK/ERK pathway may offer new therapeutic strategies.

Area Of Science

Oncology
Molecular Biology
Cell Biology

Background

Basal-like breast cancer is a subtype associated with poor prognosis.
The molecular drivers of basal-like breast cancer aggressiveness are not well understood.

Purpose Of The Study

To identify genes responsible for the aggressive behavior of basal-like breast cancer.
To investigate the role of alpha-basic-crystallin (alphaB-crystallin) in basal-like breast cancer.

Main Methods

Gene expression profiling of breast tumors.
Overexpression and RNA interference studies in human mammary epithelial cells (MECs).
In vivo studies using mouse xenograft models.

Main Results

Alpha-basic-crystallin (alphaB-crystallin) is highly expressed in basal-like tumors and predicts poor patient survival.
AlphaB-crystallin overexpression transforms MECs, inducing neoplastic-like changes and promoting anchorage-independent growth, migration, and invasion.
The MEK/ERK pathway is constitutively activated by alphaB-crystallin, and its inhibition reverses the transformed phenotype.

Conclusions

Alpha-basic-crystallin (alphaB-crystallin) is a novel oncoprotein in basal-like breast cancer, independently predicting shorter survival.
The MEK/ERK pathway is implicated as a potential therapeutic target for basal-like breast tumors.

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