The molecular and cellular biology of HER2/neu gene amplification/overexpression and the clinical development of herceptin (trastuzumab) therapy for breast cancer.

摘要: Proto oncogenes represent a family of genes which when activated have been shown to play role in the pathogenesis number malignancies vertebrate species including humans.1,2 In physiologic states these same are known normal cell growth control and differentiation. The HER2/neu gene is member Type I receptor tyrosine kinase (RTK) group one subfamilies proto oncogene encodes 185kD surface membrane protein. This has localized chromosome 17q21,1 encoded protein expressed wide variety tissues skin, oral mucera, breast, ovary, endometrium, lung, liver, pancreas, small large bowel, kidney, bladder central nervous system as well some connective tissues.4–5 exact physiological not completely understood, but like other it believed an important signaling cellular proliferation differentiation processes. Current data suggests that forms hetero-dimers with members RTKI (such HER 1, HER3 HER4 response various ligands heregulins.6–8 Activation results increase its activity turn initiates signal transduction resulting either and/or differentiation, depending on ligand conditions.9–14 human breast cancers, non-inherited alteration occurs this 25–30% cases.