The TGF-beta antibody and breast cancer research

According to the American Cancer Society,around 250,000 cases of breast cancer are diagnosed in the US each year,40,000 of which are terminal.Thanks to advances in molecular biology, antibody suppliers now have a large catalog of antibodies targeting breast cancer genes,which researchers can use to develop novel cancer therapies.However,the outcome is highly dependent upon the type of tumor.The survival rate is much lower with tumor cells which metastasize,such as basal-like breast cancer (BLBC) cells.

Mammary metastasis is dependent upon epithelial-to-mesenchymal transition, or EMT, a process by which epithelial cancer cells adapt to become highly motile mesenchymal-like breast cancer cells (MLBCs), migrating to secondary locations. Recently, a lot of antibody studies have focused on TGF-beta, a protein known to induce EMT. In milk ducts, TGF-beta induces EMT by suppressing epithelial genes and inducing mesenchymal protein expression. Intravasation then occurs, allowing MLBCs to enter blood vessels and migrate to pulmonary epithelia, where they proliferate into secondary tumors.

It is thought EMT is dependent upon type II TGF-beta receptor binding, with subsequent type I receptor transphosphorylation (exchange of phosphate groups) and phosphorylation of Smad2 and Smad3. Phospho-Smad 2/3 then forms a trimeric complex with Smad4, translocating to the nucleus and initiating expression and suppression of EMT genes via interaction with various transcription factors, activators, and suppressors. Recent antibody research by J.F. Santibáñez and others has suggested EMT also uses other signalling pathways, involving the MAP Kinases, Rho GTPases, and PI 3-Kinase/Akt.

In 2010, M. de Graauw et al reported overexpression of AnxA1, an actin regulatory protein, in BLBC cell lines, but not in luminal-like cancer cells. Antibody assay results suggested AnxA1 could modulate TGF-beta signalling by regulating Smad2 phosphorylation and Smad4 translocation. Recently, Araki et al studied the interaction of TGF-beta with the p53 tumor suppressor. It was seen that in the presence of Smad3/4, TGF-beta increased expression of the human E3 ubiquitin ligase HDM2.We at Novus Biologicals have an extensive range of TGF, Smad and associated antibodies on our antibody database.

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