Cancer

Carbonic anhydrase IX is a member of the carbonic anhydrase family. This family consists of catalytic enzymes capable of converting carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. This family of molecules is abundantly expressed in all mammalian tissues and helps to govern the pH in normal tissues. CAIX is very stable and found in the membrane. It is also one of the most hypoxically-inducible genes, thus establishing its application as a reliable and consistent hypoxia histochemical marker.

FOXO1 belongs to the very large Forkhead family of transcription factors which contain a conserved distinct DNA-binding domain known as the Forkhead Box, or FOX. The Forkhead domain is a 100 amino acid long motif capable of binding and bending DNA, and is also known as a “winged helix”. Forkhead family members are involved in a very diverse and wide range of physiological processes from cell cycle, apoptosis, and oxidative-stress resistance. The “O” class of proteins in particular are all regulated by the insulin/PI3K/AKT pathway.

The SOX gene family encodes a group of highly conserved transcription factors defined by the presence of a conserved high motility group (HMG) DNA-binding domain. They are involved in embryonic development regulation and cell fate determination. All SOX proteins have a single HMG box and bind linear DNA in a sequence-specific manner, resulting in the bending of DNA through large angles. This bending opens the DNA helix for some distance, which may affect the binding and interactions of other transcription factors.

Notch1 is a member of the Notch family of Type 1 single-pass transmembrane proteins that share an extracellular domain of multiple epidermal growth factor-like (EGF) repeats. Notch family members play key roles in a variety of developmental processes via the regulation of cell fate. These processes include cell-fate determination, proliferation, and cell contact-dependent signaling. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes a key development intercellular signaling pathway.

NUT has been found to fuse with bromodomain-containing proteins 3 and 4 (BRD3 and BRD4) in NUT midline carcinoma (NMC), a very rare, extremely aggressive, and genetically defined human cancer. NMC has recently been designated as a sub classification of poorly differentiated squamous cell carcinoma. In the majority of NMCs (~75%), most of the coding sequence is fused to form chimeric genes that encode BRD-NUT fusion proteins.

VEGFR-2 is a family member of the vascular endothelial growth factor (VEGF) family of membrane receptor tyrosine kinases. It is a key regulator of the process of angiogenesis that takes place during fundamental developmental processes such as embryogenesis, skeletal growth, and reproductive functions. Like other growth factor receptors, upon ligand binding, VEGFR2 dimerizes and is autophosphorylated on multiple tyrosine residues.

Ep-CAM is a monomeric transmembrane glycoprotein that is found exclusively on every epithelial cell membrane and a variety of epithelial carcinomas and cancer-initiating cells. It mediates calcium-independent cell-cell adhesion. Because Ep-CAM is overexpressed in a variety of human carcinomas it is both a valuable marker as well as a potential therapeutic target for human solid tumors. The adhesion properties of this molecule marker are dependent upon its two epidermal growth factor-like repeats within its extracellular domain coupled with a cysteine-poor region.

TNF alpha is a multifunctional proinflammatory cytokine that is part of the tumor necrosis factor (TNF) superfamily. It is mainly secreted by macrophages and causes tumor necrosis when injected into tumor -earing mice. It exists as a multimer of two, three, or five noncovalently linked units. TNF alpha is closely related to the 25kD Tumor Necrosis Factor beta (TNF beta, or lymphotoxin), and both proteins share the same receptors and cellular functions. TNF alpha binds and functions through the TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR receptors.

CRLF2 has been reported as an important factor that drives dendritic cell maturation and activation. It was originally shown to participate in the positive selection of regulatory T-cells, maintenance of peripheral CD4+ T-cell homeostasis, and induction of CD4+ T cell-mediated allergic reactions. CRLF2 binds to its receptor with low-affinity; high-affinity binding is facilitated by the presence of IL-7R-alpha to form a functional heteromeric complex.

The thymidine synthetic nucleoside analogue bromodeoxyuridine (BrdU) has a long, colorful history of repeated use in molecular and cytokinetic studies, as detailed in reviews by Vanderlaan and Dolbeare (1,2).  Because BrDU is only incorporated into newly synthesized DNA in actively replicating S-phase cells, it allows for accurate and comprehensive quantitation of the pattern, rate, and progression of cell proliferation.