Underlying Molecular Interconnections of the Estrogen Receptor alpha and Associated Factors involved in Breast Cancer Development: the Way to New Therapeutic Approaches

The importance of Estrogen Receptor alpha (ERa) in breast cancer development is established. Assessment of molecular mechanisms regulating its expression and action have drastically improved the diagnosis and treatment of the disease, stressing the importance to pursue experimental investigations in this medical field. In this context, the relationship between the molecular conformations of the receptor in terms of ligand binding and co-regulators recruitment ability on the one hand, and the events contributing to cell growth or apoptosis on the other, seems of peculiar interest. The known inverse connection between levels of ERa and the cell growth maker Ki 67, which respectively decrease and increase with the progression of the disease, supports this concept. The complementary connection of this relationship with the differentiation status of the tumors (grading level), suggests the presence of mechanisms involving multiple factors, which identification would be of major importance for diagnosis and therapy improvement. In fact, this perspective might not be restricted to the wild-type 67K Da receptor, it would also concern variants emerging at the stage of bad prognoses, such as the ERa36 expressed in “triple-negative” carcinomas.

We postulated that an overview of actual investigations on this topic might palliate some conceptual gaps concerning breast cancer development. Such a task would not be restricted to intracellular interactions, it may also be relevant to extracellular autocrine and paracrine regulatory procedures. Hence, we decided to invite colleagues to report their contributions in these fields in an attempt to cooperatively elaborate regulatory models for the design of new therapeutic guidelines. This task, based on a compilation of all reported data, is the finality of our editorial charge; of course, we welcome and appreciate spontaneous contributions as well.

Submissions covering a range of subjects will be considered, given the numerous molecular events relevant to this theme. Reports on the following topics would nevertheless be especially welcome:
- Ligands/coregulators-induced ERa conformational changes,
- ERa/cyclins turnover rates changes,
- Implication of the ubiquitin - proteasome system,
- Congruence of sequential of actions of ERa-mediated signal transductions and transcriptions,
- Extracellular release of peptides issued from ERa and co-regulators proteolysis contributing to auto- / paracrine regulations,
- Natural anti ERa antibodies with promoting or antagonistic activities,
- ERa variants as well as ERb,
- Drug design including protacs, in a therapeutic perspective.