Both and are closely located on q

Both and are closely located on 17q21, a region frequently deleted in sporadic breast cancers. For many years, BRCA1 has attracted much more attention in breast cancer than BECN1. encodes a multifunctional protein that plays key roles in DNA repair, over at this website control and transcriptional regulation (). Mutations in are well known to be responsible for the development of familial breast cancer. Although dysfunction has been linked also to basal-like breast cancer, it is important to note that it is mainly based on studies from familial cases with mutation. These cancers shared many phenotypes and gene expression signature associated with basal like breast cancers, suggesting similarities in pathogenic mechanisms (). Although these have been corroborated by some studies in sporadic cancers, controversy still exists among different studies (). BECN1 is an essential regulator of autophagy. , with its close proximity with , is frequently co-deleted with (). Given that it is a haplo-insufficient tumour-suppressor, its co-deletion with may also contribute to mammary tumorigenesis and cancer characteristics attributable to BRCA1 dysfunction. However, its role in breast cancer remains debatable and may depend on cellular context. Mono-allelic deletion of in C67/B6 mice has led to the formation of spontaneous lung and liver cancers as well as lymphoma but only mammary hyperplasia (). However, different results were obtained from other breast cancer models. In - or -driven mammary tumorigenesis, there are no effects of monoallelic deletion of (); whereas it delays tumour formation due to mammary gland-specific biallelic deletion in a wild-type background (). In contrast, monoallelic loss can promote mammary tumour formation following parity and in -driven oncogenesis (). The findings may indicate that the interactions of BECN1 with various cellular pathways can result in different consequences. Regarding the relationship of with specific breast cancer subtypes, so far, there is very limited information available. Of note, in mouse model, the tumour developed has been shown to exhibit basal cytokeratin upregulation as well as augmentation of mammary progenitor cell activities, i.e. characteristic of basal-like breast cancer (). It is also interesting to note that there could be some synergies in functional roles of BECN1 and BRCA1. As for BRCA1, recent findings have suggested the involvement BECN1 in the maintenance of genomic integrity () and regulation of oestrogen receptor signalling (). In all, BECN1 could have potential significance in breast cancers that have not been fully appreciated previously. However, its precise roles in breast cancer biology remain elusive. Breast cancer is a heterogeneous disease comprised of different subtypes with different underlying biology. As shown by the different findings from various model systems, functional impacts of alteration could be context dependent. Examination and evaluation of large datasets in light with signalling pathway alterations within different breast cancers will be necessary to have a clear understanding of clinical impacts as well as biology of alterations. In fact, when Tang et al. stratified expression into three expression levels, the intermediate groups did not show a consistent outcome in different subgroups of breast cancers, possibly reflecting the different biology underlying this group in contrast to the low and high expressing cases. The clinico-pathological characteristic and nature of this group in comparison with the others remains to be explored, in particular in different subgroups of breast cancers. Findings from Tang et al. suggested the prognostic implication of mRNA contributed to the pathogenesis of breast cancer. However, the application of mRNA prognostic marker in routine clinical practice still has some limitations. It would be interesting to explore whether similar findings could be also observed with BECN1 protein expression. While transcriptional deregulation of appears to play a significant role in breast cancer pathogenesis, other post-transcriptional regulatory mechanisms could be involved in BRCA1 deregulation, for example, aberrant subcellular localisation and deregulation in protein expression of BRCA1 (). The contribution of BRCA1 deregulation in the pathogenesis of breast cancer cannot be ruled out. Evaluation on their protein expressions and other regulatory mechanisms will be essential to draw a more definitive conclusion on their respective significance in breast cancer.