We have a large antibody database focussing on the area of cancer research. Recently, much interest has focussed on TGF-beta, a Transforming Growth Factor which plays an important role in a number of diseases.
TGF-beta exists as three very similar isoforms, and is encoded as a large protein precursor, which is activated by proteolytic cleavage and dimerization. Primarily involved with cell proliferation and differentiation, it is known to induce epithelial-to-mesenchymal transition (EMT) in tumours. EMT is associated with the most invasive tumour subtypes, for example basal-like breast cancers (BLBCs).
EMT determines the invasive nature of tumour cells by increasing their ability to migrate to other areas (metastasize). In EMT, epithelial cancer cells acquire the migratory properties of mesenchymal cells. The reverse process, MET or mesenchymal-to-epithelial transition, allows the cells to invade secondary areas.
The role of TGF-beta as an inducer of ENT is well documented. The signalling cascades for this remain uncertain; however, the classic TGF-beta signalling pathways are well understood. Signalling occurs following binding of the protein to type ll TGF-beta receptors and transphosphorylation (phosphate transfer) between type l receptors, followed by Smad2 and Smad3 phosphorylation. These form a trimer with Smad4, translocating to the nucleus and interacting with transcription factors and other proteins to promote expression of mesenchymal proteins. Recently, K. Aquilano, H.K Charlton and others have demonstrated that non-Smad signalling pathways, for example ERK MAP Kinase activation, may promote EMT via TGF-beta activation.
In 2010, antibody studies by M. de Graauw and J.F Santibanez et al suggested the actin regulator protein AnxA1 could play a functional role in basal-like breast cancers, demonstrating a role in MET morphology and a possible regulatory function in TGF-beta signalling. In human cancer patients, AnxA1 expression was significantly higher in BLBC tumours. Another antibody study, by Araki et al, looked at the effect of TGF-beta on the tumour suppressor protein p53, noting a marked correlation between activation of Smad3 and HDM2 levels in tumour cells. HDM2 is involved in the ubiquitinisation and degradation of p53.
We at Novus Biologicals are one of the leading antibody suppliers for cancer research.
Posts tagged ‘Antibodies’
Antibody suppliers provide a wide range of reagents for use in cancer research. One of the most common areas of study is apoptosis, or programmed cell death, a complicated cascade involving many individual proteins and pathways. We at Novus Biologicals have an extensive apoptosis antibody catalogue, with over 8000 proteins products. Proteins targeted include Apaf-1; Bcl-2; Bax; FAS and the caspases.
Apoptosis is essential to normal development and maintenance of the organism. Cells have a finite life span, and there is a constant program of cellular replacement and removal which is very finely controlled. Apoptosis also deals with cells considered a threat to the organism, such as those infected by viruses, those which have fulfilled an immune system function and those with DNA mutations or which identify themselves as cancer cells. Apoptosis is an important part of cancer research, since resistance to programmed cell death is known to be a key element in the survival of tumour cells.
Malignancies develop in response to delayed or inhibited apoptosis. Cells will then live longer, and often grow faster, than normal cells, allowing tumours to develop. This is often due to defects in the cell signalling pathways, which can also make tumour cells more resistant to chemotherapy drugs. Thus a large amount of research is done in overcoming resistance to apoptosis, or in stimulating apoptotic pathways to encourage programmed cell death of cancer cells.
The caspases belong to the cysteine protease enzyme family, and play an essential role in apoptosis. They form three groups: initiator, effector and cytokine processor caspases, which when activated initiate a complex enzyme cascade. Disruption of this mechanism is a key factor in many cancers.
Recently, we announced an exciting new development to our antibody database, becoming the sole distributor for the SDIX Genome Antibody Technology range. A revolutionary new method of producing highly targeted immunoglobulins, it includes a wide range of apoptosis reagents, including BCL-2, BAX and caspase antibodies