Navigation Links
Cell study finds receptor can fight tamoxifen-resistant breast cancer cells

A receptor that is present in the nucleus of cells can, when activated, slow the growth of tamoxifen-resistant breast cancer cells, a new study found. The study built on the recent discovery that farnesoid X receptor (FXR) a nuclear receptor found mainly in the liver is found in breast cancer tissue. Although previous research showed that FXR can slow proliferation of breast cancer cells, it was not known whether it could do the same with tamoxifen-resistant cells.

The research is part of an effort to overcome tamoxifen resistance in breast cancer patients who are good candidates for tamoxifen treatment, but who either do not respond to the drug or who develop resistance over time. These findings suggest that FXR, when activated by chenodeoxycholic acid (a bile acid) or GW4064 (a synthetic), can slow the proliferation of breast cancer cells that are tamoxifen resistant, said one of the study's authors, Cinzia Giordano.

Giordano, Donatella Vizza, Salvatore Panza, Ines Barone, Daniela Bonofiglio, Suzanne A. Fuqua, Stefania Catalano and Sebastiano And carried out the study, "Activated farnesoid X receptor inhibits growth of tamoxifen resistant breast cancer cells." The researchers are from the University of Calabria in Italy, except Dr Fuqua, who is with Baylor College of Medicine in Houston.

The study will be presented at the Experimental Biology 2010 conference on Saturday, April 24 and again on Tuesday, April 27. The American Society for Investigative Pathology is sponsoring the sessions. The conference takes place in Anaheim April 24-28.

Maintaining tamoxifen sensitivity is key

Tamoxifen is an effective breast cancer treatment for patients who are estrogen receptor positive the majority of breast cancer patients. Breast cancer cells, which need estrogen to grow, have estrogen receptors to allow them to take in estrogen. Tamoxifen interferes with the cancer cells' ability to get estrogen and in the process inhibits the ability of the cancer cells to proliferate.

Tamoxifen generally works well on breast cancer cells that are estrogen receptor positive, but some cells that are receptor positive either do not respond to the drug, or they become resistant. When tamoxifen is unable to inhibit breast cancer cell growth in estrogen-positive patients, it is called hormonal resistance.

Recent studies had already shown that FXR, commonly found in the liver, induces death in breast cancer cells. The researchers wanted to find out if FXR, when activated in breast cancer tissue, would control the growth of tamoxifen-resistant cells. They used two types of receptor-positive breast cancer cells:

  1. MCF-7, which is sensitive to tamoxifen; that is, tamoxifen keeps these cancer cells in check
  2. MCF-7TR, which is resistant to tamoxifen; that is, the drug does not keep the cancer in check.

The research team activated FXR with either a bile acid, chenodeoxycholic acid, or a synthetic, GW4064. Once FXR was activated, the researchers found that it reduced the survivability of both the tamoxifen-sensitive and tamoxifen-resistant cells. In fact, FXR inhibited the tamoxifen-resistant cancer cells (MCF-7TR) more than the tamoxifen sensitive cells.

How does it work?

The researchers found that FXR inhibited expression of a growth factor signaling mediator -- human epidermal growth factor receptor 2 (HER2). HER2 is present in 20% of breast cancers and is associated with enhanced malignancy and poorer prognosis. The over-expression of HER2 on the breast cancer cell surface is believed to disrupt the cell's ability to control growth, Giordano said, allowing the cells to rapidly proliferate. FXR seems to inhibit that process.

Why would FXR work better against MCF-7TR, the tamoxifen-resistant cells? Part of the explanation may be that MCF-7TR relies more on HER2, and FXR targets HER2, Giordano said. That would make the tamoxifen-resistant cancer cells more vulnerable to activated FXR, she said.

"This is an 'in vitro' preclinical study, but of course the next step will be to test this in vivo using mice implanted with tamoxifen-resistant breast cancer cells," said Giordano.


Contact: Donna Krupa
Federation of American Societies for Experimental Biology

Related medicine news :

1. Study examines global availability of treatment involving transplantation of blood stem cells
2. Study finds that drugs used for treatment of influenza in pregnancy appear to be safe
3. Comparative-effectiveness study confirms new treatment for diabetic macular edema
4. CureTogether Announces Online Autism Treatment Study
5. LA BioMed awarded research grant to study HIV prevention gel
6. Study Makes Strides in Understanding Ovarian Cancer
7. Brown Rice Tied to Better Heart Health in Study
8. NIH study confirms location of stem cells near cartilage-rich regions in bones
9. Immune cells predict success of head and neck cancer treatment, U-M study finds
10. Noncardiac Chest Pain May Warrant More Management: Study
11. SGIC Study Finds Drivers Are Losing Their Cool At School
Post Your Comments:
(Date:6/26/2016)... ... 2016 , ... Brent Kasmer, a legally blind and certified personal trainer is helping to develop ... The fitness app plans to fix the two major problems leading the fitness industry today:, ... all type program , They don’t eliminate all the reasons people quit their ...
(Date:6/25/2016)... ... 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due to ... a new, often overlooked aspect of head lice: the parasite’s ability to live away from ... common occurrence, but a necessary one in the event that lice have simply gotten out ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... non-athletes recover from injury. Recently, he has implemented orthobiologic procedures as a method ... —Johnson is one of the first doctors to perform the treatment. Orthobiologics are ...
(Date:6/24/2016)... ... June 24, 2016 , ... Those who have experienced ... feelings, many turn to unhealthy avenues, such as drug or alcohol abuse, as a ... has released tools for healthy coping following a traumatic event. , Trauma sufferers tend ...
(Date:6/24/2016)... ... 2016 , ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida ... their peers for this recognition are considered among the top 2 percent of lawyers ... as members of this year’s Legal Elite Hall of Fame: Miami Shareholders Mark ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016   Bay ... Rehabilitation Network,s Dean Center for Tick Borne ... Medicine and Rehabilitation, MIT Hacking Medicine, University of ... Innovation, today announced the five finalists of ... Lyme disease.  More than 100 scientists, clinicians, researchers, ...
(Date:6/24/2016)... Dehaier Medical Systems Ltd. (NASDAQ: ... and sells medical devices and wearable sleep respiratory products ... cooperation agreement with Hongyuan Supply Chain Management Co., Ltd. ... 20, 2016, to develop Dehaier,s new Internet medical technology ... will leverage Hongyuan Supply Chain,s sales platform to reach ...
(Date:6/24/2016)... LEXINGTON, Mass. , June 24, 2016   ... specialty pharmaceutical company developing innovative inhaled drugs, announced today ... when Russell Investments reconstituted its comprehensive set ... 2016. "This is an important milestone for ... "It will increase shareholder awareness of our progress in ...
Breaking Medicine Technology: