Protein kinases in mammary gland development and cancer

Protein kinases, the enzymes responsible for phosphorylation of a wide variety of proteins, are the largest class of genes known to regulate growth, development, and neoplastic transformation of mammary gland. Mammary gland growth and maturation consist of a series of highly ordered events involving interactions among several distinct cell types that are regulated by complex interactions among many steroid hormones and growth factors. The mammary gland is one of the few organ systems in mammals that complete their morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. Thus, the mammary gland is an excellent model for studying normal development and the early steps of tumor formation. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy. Numerous experimental and epidemiological studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression and functions of protein kinases. Perturbations in the regulated expression or function of protein kinases or their associated signaling pathways can lead to malignant transformation of the breast. For example, overexpression of several receptor-tyrosine kinases, including human epidermal growth factor receptor and HER2/Neu, has been shown to contribute to the development of breast cancer. Since receptor-tyrosine kinases regulate several essential processes such as mitogenesis, motility, invasion, cell survival, and angiogenesis, targeting receptor-tyrosine kinases may have important implications in designing strategies against breast cancer.