Mecanismos implicados en el desarrollo del cáncer de mama. Estudios en células epiteliales de ratón en cultivo primario y en la línea celular mcf-7

Resumen

Almost 50% of all breast cancers express high levels of oestrogen receptor (ER) and the majority of them may cure due to selective and non selective oestrogen antagonists'treatment, albeit there are cases of endocrine-resistant cancers which do no respond at the regular treatment. ER exercises its transcriptional activity by means of the interaction with coactivators such the family of the nuclear receptors p160-SRC. AIB1 is the third member of this family of nuclear receptors and takes part into the ER's transcriptional complex "in vivo". Surprisingly, AIB1 is overexpressed in a wide range of cancers, including breast cancer, and it correlates with the expression of ER. This data explains our interest in ascertaining the eventual AIB1's molecular mechanisms in which it may be involved in to promote or strengthen the breast cancer's development. Our attention approaches AIB1's involvement in fundamental mechanisms of tumoral progression such as cancer cells'proliferation, migration and differentiation. In the present investigation work we propose for the first time that AIB1 may act in a possible dual manner, according to the cellular context. We demonstrate that apart of its involvement in cell proliferation, AIB1 takes part in a direct or indirect way into mechanisms related to shapening the extracellular matrix (MEC), cellular differentiation by E-cadherin's control and cellular migration. We propose that AIB1 may be involved into the TGF-beta signalling pathway and thus mediate the functioning of these cellular processes.