They discover a cellular mechanism that impedes the effectiveness of the treatment of breast cancer.

-researchers from CIC bioGUNE, the Massachusetts General Hospital and Harvard Medical School becoming a complex cellular mechanism activated by a protein – HOXB9 – derived an obstacle to the effectiveness of radiation

– the study was published recently in the journal Proceedings of the National Academy of Sciences (PNAS)

Bilbao, 2011-October breast cancer still hogging the attention of the scientific community worldwide. As a result, increasingly have more knowledge about the behavior of tumor cells, as well as its relations with the microenvironment that surrounds them. While there are still many unknowns by reveal.

A new study carried out by the laboratory of Dr. María Vivanco, researcher at the unit of Molecular Biology and mother cells of the Centre for research in BioScience, CIC bioGUNE, in collaboration with groups of Zou and Maheswaran Boston doctors, has unveiled one of these unknowns, as a complex cellular mechanism is explains how a protein – known as HOXB9 – manages to avoid the attacks of anti-cancerígenos treatments, such as radiation and prevents that such therapy has the necessary efficiency in certain cases of breast cancer.

The study, published recently in the journal Proceedings of the National Academy of Sciences (PNAS), and which also helped researchers from the Massachusetts General Hospital and the Harvard School of medicine, shows that cells that express higher levels of the HOXB9 transcription factor have a greater ability to survive the radiation that is offered as therapy for patients with breast cancer.

A complex mechanism initiated by the protein that manages to activate an entire chain of cellular processes that involve different proteins has decrypted – as the ATM kinase, among others – and, ultimately, allowing some cancer cells are more resistant to treatments to prevent the spread of the disease. According to the DRA. Vivanco, when the tumor is exposed to radiation therapy, it causes damage to the DNA – phenomenon is known as double-stranded DNA breaks-, giving rise to a cellular response that tries to repair the damage caused in the DNA using another mechanism – called DNA damage response – ”, through the activation of ATM kinase. In this way, it induces the stop of the cell cycle and promotes DNA repair to maintain chromosomal stability.

HOXB9 expression results in an increase in the survival of cells that have been exposed to radiation. This increased resistance is possible due to the acceleration of the response to radiation and its greater ability to recovery after an injury to his DNA. On the other hand, the reduction of the levels of this protein leads to an increase in the sensitivity of cells to radiation. Furthermore, it was noted that growth factor TGFbeta (a HOXB9 diana) is also involved and that HOXB9 power through the activation of the pathway DNA repair of TGFbeta signaling.

Research published now accounts for the continuation of another study conducted last year by CIC bioGUNE, the Harvard Medical School and Massachusetts General Hospital, which already showed that this same protein (HOXB9) is on-expressed in breast cancer and their expression levels are associated with a high tumor grade.