The factor that could influence future breast cancer treatment

December 27, 2012

Australian scientists have shown in the laboratory how a 'transcription factor' causes breast cancer cells to develop an aggressive subtype that lacks sensitivity to estrogen and does not respond to known anti-estrogen therapies. The research, which has significant implications for breast cancer treatment, is published December 27 in the open access journal PLOS Biology.

Transcription factors are molecules that switch genes on or off. In this case, the transcription factor known as 'ELF5' inhibits sensitivity to estrogen very early in the life of a breast cancer cell. In 2008, Professor Chris Ormandy from the Garvan Institute of Medical Research in Sydney, Australia, showed that ELF5 was responsible for the development of breast progenitor cells into the estrogen-receptor-negative cells that produce milk in the breast during pregnancy.

In the current study, a team led by Ormandy in collaboration with Drs Maria Kalyga and David Gallego-Ortega, has shown that the same molecular decision occurs in breast cancer and that ELF5 has the ability to change an existing tumour into an estrogen-insensitive tumour.

"This work tells us that cancers which become refractory to anti- often do so by elevating their levels of ELF5 and becoming functionally estrogen receptor negative," said Ormandy.

The team has also described the genetic mechanisms by which ELF5 opposes the action of estrogen, and has shown that it is possible to alter the subtype of breast cancer by manipulating ELF5 levels in cancer cells in the laboratory.

"This raises the therapeutic option of manipulating ELF5 levels to treat breast cancer. As ELF5 is intracellular, this could possibly be done with small molecule therapies that penetrate cells and -to-protein interactions, or with small inhibitory RNAs. There is also the possibility of testing ELF5 levels in tumours to predict response to treatment and therefore guide treatment decisions."

"Our key discovery here is that by simply manipulating one transcription factor we can change the subtype of breast cancer."

Explore further: Lactation protein suppresses tumors and metastasis in breast cancer, scientists discover

More information: Kalyuga M, Gallego-Ortega D, Lee HJ, Roden DL, Cowley MJ, et al. (2012) ELF5 Suppresses Estrogen Sensitivity and Underpins the Acquisition of Antiestrogen Resistance in Luminal Breast Cancer. PLoS Biol 10(12): e1001461. doi:10.1371/journal.pbio.1001461

Related Stories

Lactation protein suppresses tumors and metastasis in breast cancer, scientists discover

October 24, 2012
A protein that is necessary for lactation in mammals inhibits the critical cellular transition that is an early indicator of breast cancer and metastasis, according to research conducted at the University at Buffalo and Princeton ...

Resistance to anti-estrogen therapy in breast cancer due to natural cell response

April 4, 2011
Most breast cancers are fueled by estrogen, and anti-estrogenic agents often work for a time to control the cancers. But many of these cancers become resistant to the drugs for reasons that are not understood, leaving patients ...

Study shows breastfeeding reduced risk for ER/PR-negative breast cancer

October 18, 2012
Breast-feeding reduces the risk for estrogen receptor-negative and progesterone receptor-negative breast cancer, according to a study conducted at Columbia University's Mailman School of Public Health. Researchers examined ...

Recommended for you

Clear link between heavy vitamin B intake and lung cancer

August 22, 2017
New research suggests long-term, high-dose supplementation with vitamins B6 and B12—long touted by the vitamin industry for increasing energy and improving metabolism—is associated with a two- to four-fold increased lung ...

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.