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NSCLC Research: Anti-Keap1 Antibody Helps Uncover Target’s Biomarker Potential

admin March 6, 2013

Guest post by Katie Griffiths

Kelch-like ECH-associated protein 1 (Keap1) is a crucial substrate adapter protein for the Cul3-RBX E3 ubiquitin ligase complex, and a key regulator of the Nrf2 cytoprotective pathway. Under normal conditions, levels of Nrf2 are constantly regulated by rapid ubiquitination and proteasomal degradation; thus the antioxidant response is continually suppressed. However, when the cell is placed under oxidative stress, key cysteine residues in Keap1 are modified inhibiting the activity of the E3 ubiquitin ligase complex. Levels of Nrf2 are allowed to stabilize and increase, leading to the induction of numerous cytoprotective genes.

Considering its key role in cytoprotection, it is no surprise the Nrf2 pathway is of considerable interest to the field of cancer biology. As a consequence, Proteintech’s anti-Keap1 antibody has played a crucial role in a number of studies relating to cancer and chemotherapy.  In particular, dysregulation of the Nrf2/Keap1 pathway has been implicated in non-small cell lung cancer (NSCLC) [1].  Sequencing of KEAP1 revealed that 50% of NSCLC cell lines carry somatic mutations in this gene, with the mutations focused in the Kelch-like region of the protein ― the region responsible for Keap1’s E3 ligase repressor activity. In these cell lines, Keap1 is unable to inhibit the ubiquitination of Nrf2, and as a result they are unable to respond successfully to oxidative stress. In 2010, a study published in Clinical Cancer Research used Proteintech’s anti-Keap1 antibody to demonstrate that dysregulated Keap1 was particularly associated with poor outcome prognosis in NSCLC [2].

Immunohistochemical staining of paraffin-embedded human lung cancer using KEAP1 Antibody 10503-2-AP (10x lens).

Immunohistochemical staining of paraffin-embedded human lung cancer using KEAP1 antibody 10503-2-AP (10x lens).

More recently, Proteintech’s anti-Keap1 antibody featured in a study published in the open-access journal PLoS One. This work successfully demonstrated that two known subtypes of NSCLC ― adenocarcinoma and squamous cell carcinoma ― can be considered as separate diseases with distinct pathogenic phenotypes [3]. This discovery naturally has considerable implications for the diagnosis and treatment of NSCLC, and their results support the idea of Keap1 as a molecular biomarker for subtypes of this disease.

The PLoS One study utilized Proteintech’s anti-Keap1 antibody to demonstrate that subtype-specific differences identifiable in the genome are also visible at the protein level through immunohistochemistry. Immunohistochemical analyses were carried out over a panel of 200+ lung tumors, and the antibody was used to identify whether Keap1 was inactivated in these cells. The results showed that dysregulation of Keap1 is a feature of adenocarcinoma, but that levels of Keap1 remain normal in squamous cell carcinoma. These results clearly identify Keap1 as a potential biomarker for identification of adenocarcinoma as a NSCLC subtype, and may have significant implications in future diagnosis and treatment of this disease.

More on Proteintech’s anti-Keap1 antibody

The anti-Keap1 antibody has also featured in a number of studies relating to cancer biology, including multiple myeloma, breast cancer and Wilms tumor, and other fields including inflammatory conditions. More details of these studies can be found in the following references: 215979222182100922215675222222062250398122629454230415492328513821498569,214827152146525121126175204272902017374219279006

Katie Griffiths

Guest Blogger profile

Katie Griffiths is a freelance scientific editor, technical writer and science communicator. She has recently graduated with a Research Masters in Structural Biology from The Institute of Structural and Molecular Biology at Birkbeck College. In her spare time she writes a blog The Molecular Circus, enthusing her readers about the molecular biology of everyday life.

 

Related Antibodies

Nrf2 rabbit polyclonal antibody (Cat no. 16396-1-AP)

Keap1 rabbit polyclonal antibody (Cat no. 10503-2-AP)

Keap1 mouse monoclonal antibody (Cat no. 60027-1-Ig)

 

References

[1] A. Singh et al., PLoS Med 3(10):e420 

[2] LM Solis et al., Clin Cancer Res 16(14):3743-53 

[3] WW Lockwood, PLoS One. 2012; 7(5): e37775 

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