Glossary

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amplification: Selective replication of a specific gene or genes disproportionate to their representation in the parent molecule, such as that occurring in specific cells in response to signals of cell development or to stress from the environment. In humans this process is seen most often in malignant cells.
angiogenesis: The induction of the growth of blood vessels from surrounding tissue into a tumor by a diffusible protein factor released by the tumor cells.
apoptosis: Also called programmed cell death, it is a signaling pathway that leads to cellular suicide in an organized manner. Several factors and receptors are specific to the apoptotic pathway. The net result is that cells shrink and develop blebs on their surface, and their DNA undergoes fragmentation.
autocrine: A mode of hormone action in which a hormone binds to receptors on, and affects the function of, the cell type that produced it.

chromogenic in situ hybridization (CISH): A method of in situ hybridization which enables detection of HER-2/neu gene copies with conventional peroxidase reaction. This method of detection differs from FISH in that CISH employes chromogenic molecules as markers, rather than fluorescent molecules.
crosstalk: Process by which different components of a given signal transduction pathway influence components of another pathway.

endosome: A cytosolic vesicle with an acidic internal pH in which certain bound ligands dissociate from their membrane-bound receptor proteins.
estrogen receptor (ER): A type of nuclear receptor consisting of a cellular regulatory protein that binds estrogens, found on nearly all cell types, but particularly in estrogen-sensitive tissues such as the uterus and breast.
exon: A coding sequence in a gene.

fluorescence in situ hybridization (FISH): In situ hybridization in which DNA probes are labeled with fluorescent tags and hybridized to metaphase or nondividing (interphase) chromosome spreads to identify and localize specific sequences.

genomic: Pertaining to the genome, the entirety of the genetic information encoded by the nucleotide sequence of an organism, cell, organelle, or virus.
growth factor: A substance made by the body that functions to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy.

heregulins: A family of ligands known to bind the HER3 and HER4 receptors, also capable of inducing phosphorylation of the p185HER-2/neu receptor.
heterodimer: A dimer consisting of unlike subunits.
homodimer: A dimer consisting of identical subunits.

immunohistochemistry (IHC): The application of antigen-antibody interactions to histochemical techniques. Typically, a tissue section is mounted on a slide and incubated with antibodies (polyclonal or monoclonal) specific to the antigen (primary reaction). The antigen-antibody signal is then amplified using a second antibody conjugated to a complex of peroxidase-antiperoxidase (PAP), avidin-biotin-peroxidase (ABC), or avidin-biotin alkaline phosphatase. In the presence of substrate and chromogen, the enzyme forms a colored deposit at the sites of antibody-antigen binding.

ligand: A molecule that binds to another molecule; used especially to refer to a small molecule that binds specifically to a larger molecule, eg, an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme.

mitogen-activated protein kinase (MAPK): Any of a group of protein-serine/threonine kinases that when activated enter the cell nucleus and catalyze the phosphorylation of serine and threonine residues in transcription factors that regulate gene expression; it is the final member of a signal transduction cascade of three protein kinases that is initiated by stimulation of a wide variety of membrane receptors and is important in the regulation of cell growth and differentiation.
mutation: A permanent transmissible change in the genetic material, usually in a single gene, although the term is sometimes used to include gross alterations in chromosomal structure.

neuregulins: A family of proteins, whose members are structurally related to epidermal growth factor, that act as specific activating ligands for the HER family.

overexpression: Excessive expression of a gene by producing too much of its effect or product.

phenotype: The observable morphological, biochemical, and physiological characteristics of an individual, either in whole or with respect to a single or a few traits, as determined by a combination of the genotype and the environment.
phosphoinositide 3-kinases (PI3Ks): A family of enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol.
phosphorylation: The metabolic process of introducing a phosphate group into an organic molecule.
progesterone receptor (PR): A protein found inside the cells of the female reproductive tissue, some other types of tissue, and some cancer cells. The hormone progesterone will bind to the receptors inside the cells and may cause the cells to grow.
proteomics: The study of the structure and function of proteins, including the way they work and interact with each other inside cells.

Rajkumar score: Scoring system based on the product of the score for the fraction of positively stained tumor cells (ranging from 0 to 4: 0 = <10% of positively stained tumor cells; 1 = 10% to 25%; 2 = 26% to 50%; 3 = 51% to 75%; 4 = >75%) and the score for staining intensity (0 to 3).
RAS: Any of a family of human proto-oncogenes related to oncogenes first identified in Harvey murine sarcoma virus (H-ras) and Kirsten murine sarcoma virus (K-ras). Mammalian cells contain three 21 kDa Ras proteins (H- K- and N-Ras) that act as GTP-binding proteins with GTPase activity, and are important in the cell cycle; specific point mutations can lead to oncogenesis.
reverse transcriptase-polymerase chain reaction (RT-PCR): A highly sensitive technique for the detection and quantitation of mRNA (messenger RNA). This technique consists of two parts: the synthesis of cDNA (complementary DNA) from RNA by reverse transcription (RT) and the amplification of a specific cDNA by the polymerase chain reaction (PCR).
RNA: A chemical found in the nucleus and cytoplasm of cells; it plays an important role in protein synthesis and other chemical activities of the cell. The structure of RNA is similar to that of DNA. There are several classes of RNA molecules, including messenger RNA, transfer RNA, ribosomal RNA, and other small RNAs, each serving a different purpose.

transactivation: Stimulation of gene transcription by a specific protein.
transphosphorylation: The exchange of phosphate groups between organic phosphates, without their going through the stage of inorganic phosphate.
tyrosine kinase: Generic name for an enzyme that phosphorylates tyrosine molecules in proteins.

vascular endothelial growth factor (VEGF): A substance made by cells that stimulates new blood vessel formation.