Too much of a good thing: Important mechanism in hormone-sensitive breast cancer uncovered

Nov 23, 2010
Fluorescence micrograph of breast cancer cells. Credit: Lutz Langbein, Deutsches Krebsforschungszentrum

In two out of three breast tumors, extraordinarily high levels of the estrogen receptor ERalpha are found. Scientists of the German Cancer Research Center have now uncovered a mechanism which causes this overproduction. This result might contribute to developing new strategies for fighting the most frequent type of cancer affecting women.

Two thirds of breast cancers are ERalpha-positive, i.e., many estrogen receptors of the ERalpha- type are found in their cells. "These molecules can interact with the estrogen hormone and, thus, even lead to cancer," explains Dr. Joerg Hoheisel; molecular biologist at DKFZ. "The connection between the levels of the alpha and the occurrence of has been known for some time now. Early-stage already produce too many of these receptors. This is associated with increased cell division, which is ultimately responsible for ," says Hoheisel.

Jointly with his coworkers, Dr. Yasser Riazalhosseini and Pedro de Souza Rocha Simonini, Joerg Hoheisel has now been able to show that a tiny little nucleic acid, a microRNA known as miR-375, causes the high receptor levels which, in many cases, lead to cancer. MicroRNAs are important intracellular signal mediators, which have a substantial influence on the effectiveness of genes. The DKFZ group discovered that miR-375 blocks the production of an enzyme which influences the production of ERalpha-receptors. Thus, high levels of miR-375 lead to production of many estrogen receptors. At the same time, elevated ERalpha-levels lead to production of more miR-375. This feedback loop further boosts the multiplication of cancer cells.

The research group headed by Joerg Hoheisel has now published the results of their experiments in the journal Cancer Research. They also present a first indication of a possible medical application of the newly gained knowledge: "We were able to block the miR-375 in ERalha-positive cells. This effectively slowed down cancer cell growth." Whether and how miR-375 will play a role in breast cancer treatment in the future is a question which Hoheisel cannot answer yet. "But we hope to be able to use our results in the future for developing new strategies against tumors with too many estrogen receptors."

Explore further: Exercising restraint to stall tumor growth

More information: de Souza Rocha Simonini P, Breiling A, Gupta N, Malekpour M, Youns M, Omranipour R, Malekpour F, Volinia S, Croce CM, Najmabadi H, Diederichs S, Sahin O, Mayer D, Lyko F, Hoheisel JD, Riazalhosseini Y.:Epigenetically Deregulated microRNA-375 Is Involved in a Positive Feedback Loop with Estrogen Receptor alpha in Breast Cancer Cells. Cancer Research 2010; DOI:10.1158/0008-5472.CAN-10-1318

add to favorites email to friend print save as pdf

Related Stories

How Does Estrogen Feed Breast Cancer Tumors?

Mar 02, 2010

(PhysOrg.com) -- A new study is providing insight into how estrogen fuels many breast cancers, and researchers say the findings could lead to new cancer-fighting drugs.

Recommended for you

Exercising restraint to stall tumor growth

2 hours ago

Many proteins undergo an assembly line-style process of glycosylation as they travel from a cellular structure called the endoplasmic reticulum (ER) to the Golgi apparatus and on through its various compartments, ...

New tool to probe cancer's molecular make-up

Aug 26, 2014

Scientists have shown how to better identify and measure vital molecules that control cell behaviour – paving the way for improved tools for diagnosis, prediction and monitoring of cancer.

Mayo Clinic offers at-home colon cancer test

Aug 26, 2014

Mayo Clinic is taking another step toward making detection of colorectal cancer as convenient as possible, announcing Monday an at-home kit that arrives and is sent back in the mail, stool sample included.

User comments : 0