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From Proteopedia

I would like the page to have a table of contents and the following main sections: Background, Structure (with a jmol image area), Function, Clinical Relevance, and References.

Background

Anterior gradient protein 2 (AGR2) is also known as Gob-4, hAG-2 and in Xenopus laevis, the African clawed toad, XAG-2 [6]. It is not only a secretory protein, it is also an endoplasmic reticulum protein responsible for the progression of metastatic cancers in humans, and in Xenopus laevis, tissue development [6]. It was first discovered in Xenopus laevis in the mucus secreting cement gland which allows for organogenesis of this organism [5]. Organogenesis is when the ectoderm, endoderm, and mesoderm develop in an organism's internal organs and other tissue differentiation such as: limb regeneration, forebrain formation and cellular differentiation and development [5]. In humans, AGR2 was discovered in a breast cancer study in which the AGR2 gene was cloned and immunohistochemical staining was used to determine its presence in the carcinoma cell lines of the cancer patients [7].

Structure

The structure of AGR2 consists of an unstructured N-terminal with a thioredoxin fold, intermolecular salt bridges and is a monomer dimer [3]. The unstructured N-terminal with the thioredoxin fold accounts for cell adhesion and the thioredoxin protein is associated with redox signaling to reduce other proteins and electron transfer signaling [3]. The intermolecular salt bridges account for stabilization and it is a monomer dimer because of its single chain structure [3].

Function

The biochemical function of AGR2 is not exactly understood [6]. However, it seems that in humans it is being overexpressed and in turn the activation of the tumor suppressor protein, p53, is inhibited [6]. The activation of p53 is essential in multicellular organisms because it regulates the cell cycle to prevent cancers from forming and metastasizing [1]. In Xenopus laevis, the opposite is the problem. The underexpression of AGR2 causes the organism to not fully develop [5].

Clinical Relevance

AGR2 can be detected in metastasizing cancer sufferers to include: prostate cancer, lung cancer, breast cancer, esophageal cancer, ovarian cancer, pancreatic cancer, etc. [4,5,6,7]. An ELISA test is used to detect AGR2 in the blood plasma of cancer patients by taking peripheral blood from circulating tumor cells [2]. Immunohistochemical staining can be used to take epithelial cells from tissues affected with cancer [2]. Polymerase chain reaction (PCR) and Western blotting have been used for pancreatic cancer cell proliferation [4]. Transformation of cell lines such NIH3T3 has also been used by transfecting the cell line and promoting tumor growth in mice but it had spread into intestinal cells by an unknown mechanism/ function of the AGR2 [5].

References

1. Boyer, R. (2006 ). Concepts in Biochemistry. Hoboken, NJ: Wiley and Sons.

2. Edgell, T. (2010). Increased Plasma Concentrations of Anterior Gradient 2 Protein are Positively Associated with Ovarian Cancer. Clinical Science, 717-725.

3. Patel, P. (2013, January 30). 2LNT. Retrieved March 30, 2013, from Proteopedia: http://www.proteopedia.org/wiki/index.php/2lnt

4. Ramachandran, V. (2008). Anterior Gradient 2 is Expressed and Secreted during the Development of Pancreatic Cancer and Promotes Cancer Cell Survival. Cancer Research, 7811-7818.

5. Wang, Z. (2008). The Adenocarcinoma- Associated Antigen, AGR2, Pormotes Tumor Growth, Cell Migration, and Cellular Transformation. Cancer Research, 492-497.

6. Wu, J. (2012). Identification, Characterization and Application of a G-Quadraplex Structured DNA Aptamer against Cancer Biomarker Protein Gradient Homolog 2. Plos One, 1-9.

7. Zhang, Y. (2007). Increased Expression of Anterior Gradient-2 Significantly Associated with Poor Survival of Prostate Cancer Patients. Prostate Cancer and Prostatic Diseases, 293-300.