HOXB7 gene promotes tamoxifen resistance

Dec 11, 2010

Many postmenopausal women with early-stage breast cancers who initially respond well to tamoxifen become resistant to the drug over time and develop recurrent tumors. Johns Hopkins Kimmel Cancer Center researchers have found that a gene called HOXB7 may be the culprit in tamoxifen resistance.

Taken by mouth, tamoxifen is used at every stage of to treat existing tumors and prevent new ones from developing. The drug works only in women whose have a protein, called the estrogen receptor, which binds to the estrogen hormone. Tamoxifen binds to this estrogen receptor and blocks estrogen's effect on fueling cancer cells.

In experiments on cancer cells, the scientists found that when the HOXB7 gene is overexpressed, as occurs in many breast cancers, tumors cells became resistant to tamoxifen. Overexpression of HOXB7 results in proteins that interact with a series of other estrogen-activated genes and proteins, including the HER2 gene, known to make breast cancers aggressive. When the scientists knocked out the HOXB7 gene in one group of breast cancer cells, HER2 activation decreased and the cells became more responsive to tamoxifen. The scientists then showed how the HOXB7-HER2 interaction works.

"HOXB7 appears crucial in orchestrating estrogen receptors, HER2 and other receptors that promote aggressive tumor growth in breast cancer cells," says senior author Saraswati Sukumar, PhD, professor of oncology and co-director of the Breast Cancer Program at Johns Hopkins. "Dialing down expression of the HOXB7 gene could stave off resistance."

Though it's not yet evident how to shut down HOXB7, Sukumar says that oncologists could potentially use the drug Herceptin to kill tumors in patients whose HER2 expression increases.

Explore further: Why we should vaccinate boys against HPV as well as girls

Provided by Johns Hopkins Medical Institutions

5 /5 (2 votes)
add to favorites email to friend print save as pdf

Related Stories

Herceptin targets breast cancer stem cells

Jul 09, 2008

A gene that is overexpressed in 20 percent of breast cancers increases the number of cancer stem cells, the cells that fuel a tumor's growth and spread, according to a new study from the University of Michigan Comprehensive ...

Clue to unusual drug-resistant breast cancers found

Oct 08, 2010

Researchers at the University of Illinois at Chicago College of Medicine have found how gene expression that may contribute to drug resistance is ramped up in unusual types of breast tumors. Their findings may offer new therapy ...

Recommended for you

Why we should vaccinate boys against HPV as well as girls

2 hours ago

Gillian Prue, from the School of Nursing and Midwifery at Queen's University of Belfast, says that the human papillomavirus (HPV) infection is common in men and can lead to genital warts and the development of some head and ...

Generation of tanners see spike in deadly melanoma

14 hours ago

(AP)—Stop sunbathing and using indoor tanning beds, the acting U.S. surgeon general warned in a report released Tuesday that cites an alarming 200 percent jump in deadly melanoma cases since 1973.

Penn team makes cancer glow to improve surgical outcomes

14 hours ago

The best way to cure most cases of cancer is to surgically remove the tumor. The Achilles heel of this approach, however, is that the surgeon may fail to extract the entire tumor, leading to a local recurrence.

User comments : 0