Research just published online in the "Journal of Biological Chemistry" identifies a new molecule involved in the regulation of oestrogen receptors (ER) expression in breast cancer.
Oestrogen is an hormone known to affect directly the survival and growth of breast cancer, and its activity is mediated through ER, which are, not only important prognostic factors in the disease, but also involved in the resistance to therapy observed in many of these tumours. The discovery, by elucidating part of the mechanism behind ER, can help to understand better breast cancer, and, in consequence, also the development of new and better therapies for the disease.
Breast cancer is still the most common malignancy among women with half a million deaths every year and one in nine of all females in the western world developing it sometime in their lives. Oestrogen is the major female sex hormone, crucial for the normal sex development and functioning of female organs and tissues, but also with a crucial role in the survival and development of many breast tumours. The hormone acts by binding to specific ER (ER-alpha and ER-beta) in a lock-and-key-mechanism that results in the activation, on the target tissue, of genes involved in cell survival and proliferation.
The role of oestrogen in cancer was first noticed about 100 years ago when researchers observed that removal of the ovaries – the major place for oestrogen production - in women with breast cancer substantially increased their chance of survival. We know now that this effect results from the fact that about 75% of human breast cancers are ER positive (mostly ER-alpha) and, as result, their grow and survival is directly dependent on oestrogen. This is also why men, that do not have ovaries and have much less oestrogen, present much lower breast cancer rates in comparison to women.
But to have ER-positive breast cancer is not only bad news since this type of tumours has the best prognosis, most probably because the hormonal therapies used in these cases (which disrupt oestrogen-ER activation) can be very effective.
Nevertheless, after an initial period of response many ER-positive tumours develop treatment resistance - even if in most of cases they maintain their oestrogen receptors - leading to disease relapses. This is believed to result from “over-activation” of ER, and consequent by-pass of the hormonal therapy effect, by growth factors, another type of hormones capable of activate ER. These cases, together with the 25% of breast tumours that are ER-negative, present a major challenge to an effective clinical management of the disease. As result it is crucial to understand the molecular and cellular mechanisms behind oestrogen receptors expression and activity for a wider and more effective breast cancer therapy.