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14-12-2010 | Oncology | Article

TNXL2 key regulator of breast cancer cell growth

Abstract

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MedWire News: The redox protein thioredoxin-like 2 (TXNL2) controls the growth and metastasis of human breast cancer cells by regulating levels of reactive oxygen species (ROS) and nuclear factor kappa B (NF-κB) activity, study findings indicate.

These findings suggest that TXNL2 "could be a target for treatment of breast cancer," remark study authors Xiaojiang Cui (John Wayne Cancer Institute, Santa Monica, California, USA) et al.

TXNL2 was recently identified by the researchers, who hypothesized that it may play a role in antagonizing oxidative stress in cancer cells.

"Cancer cells have an efficient antioxidant system to counteract their increased generation of ROS," they explain.

"However, whether this ability to survive high levels of ROS has an important role in the growth and metastasis of tumors is not well understood," they add.

Cui and team therefore aimed to determined how TNXL2 contributes to the regulation of the cellular redox state in cancer cells.

First they compared the expression levels of TXNL2 in normal breast tissue and breast cancer tissue: TXNL2 messenger RNA levels were significantly higher in breast cancer tissue than in normal breast tissue.

The team then inhibited TXNL2 in human breast cancer cell lines in vitro and observed increased ROS levels and reduced NF-κB activity, which resulted in inhibition of cancer cell proliferation, survival, and invasion.

In addition, TXNL2 inhibition in human breast cancer cells inhibited tumorigenesis and metastasis when transplanted into immunodeficient mice.

Finally, analysis of tumor samples from patients with primary breast cancer demonstrated that enhanced TXNL2 expression correlated with metastasis to the lung and brain, and with decreased recurrence-free, distant metastasis-free, disease-specific, and overall survival.

"Thus, TXNL2 may serve as a prognostic marker for breast cancer metastasis and survival," Cui and co-authors remark.

They conclude that their results may have significant clinical implications. However, "further investigation is warranted to determine whether targeting TXNL2 may be an effective approach to induce ROS in cancer cells."

The study findings are published in the Journal of Clinical Investigation.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Laura Dean

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