The new truncated somatostatin receptor variant sst5TMD4 is associated to poor prognosis in breast cancer and increases malignancy in MCF-7 cells.

Somatostatin receptors (sst1-5) are present in different types of tumors, where they inhibit key cellular processes such as proliferation and invasion. Although ssts are densely expressed in breast cancer, especially sst2, their role and therapeutic potential remain uncertain. Recently, we identified a new truncated sst5 variant, sst5TMD4, which is related to the abnormal response of certain pituitary tumors to treatment with somatostatin analogs. Here, we investigated the possible role of sst5TMD4 in breast cancer. This study revealed that sst5TMD4 is absent in normal mammary gland, but is abundant in a subset of poorly differentiated human breast tumors, where its expression correlated to that of sst2. Moreover, in the MCF-7 breast cancer model cell, sst5TMD4 expression increased malignancy features such as invasion and proliferation abilities (both in cell cultures and nude mice). This was likely mediated by sst5TMD4-induced increase in phosphorylated extracellular signal-regulated kinases 1 and 2 and p-Akt levels, and cyclin D3 and Arp2/3 complex expression, which also led to mesenchymal-like phenotype. Interestingly, sst5TMD4 interacts physically with sst2 and thereby alters its signaling, enabling disruption of sst2 inhibitory feedback and providing a plausible basis for our findings. These results suggest that sst5TMD4 could be involved in the pathophysiology of certain types of breast tumors.

"New" molecular taxonomy in breast cancer

Advances in the analysis of expression profiles, using genomic techniques, have revealed the high heterogeneity present in breast cancers. These approaches have served to identify different breast cancer subgroups with specific molecular characteristics that could sub-classify these tumours as carcinomas expressing hormone receptors, denominated Luminal subtype, and tumours with negative expression of hormone receptors, the Basal and HER2+ phenotypes. Therefore, during recent years, identification of markers characteristic of each subtype has been the focus of many research groups. All of these breast tumour subtypes probably have specific clinical and morphological features; however, this hypothesis needs to be confirmed by analysing more homogenous series. Although this "new" classification has limitations, it could be useful in the clinical practice, allowing not only a more accurate prognosis in breast cancer patients but also a selective treatment for each predefined subtype (AU)

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