Integrating signals between cAMP and MAPK pathways in breast cancer.
Breast cancer is one of the most common malignancies in Western society. Localized breast cancer, before it spreads, can be cured by surgery. However, the high mortality rate associated with breast cancer is due to a propensity of the tumor to metastasize when the primary tumor is small or undetectable. Although steroid receptor status has been recognized as the most precise predictor of response to hormone therapy, a significant number of tumors expressing these receptors metastasize and patients do not respond to the antihormone therapy. The mechanism leading to breast cancer progression and resistance to the hormone therapy is not completely understood at the present time. Compelling evidence shows that hormone-bound steroid receptors in breast cancer cells activate complex signaling networks, which include MAPK- and G protein-dependent pathways. These responses, which occur within seconds or minutes after steroid administration, are not due to changes in gene expression. Depending on cell systems, steroid activation of these networks leads to different and profound effects on extra nuclear and nuclear events. In such a way steroids foster cell cycle, reduce apoptosis and stimulate cell migration of target cells. All these processes are deregulated in breast cancer. In this review we will discuss new aspects of signaling pathways activated by steroids and their integration with other pathways in breast cancer. Recent findings on the discovery of compounds specifically interfering in such a complex network will be presented.
Castoria
Gabriella
G
Department of General Pathology, II University of Naples, Naples, Italy. gabriella.castoria@unina2.it
Migliaccio
Antimo
A
D'Amato
Loredana
L
Di Stasio
Rosina
R
Ciociola
Alessandra
A
Lombardi
Maria
M
Bilancio
Antonio
A
Di Domenico
Marina
M
de Falco
Antonietta
A
Auricchio
Ferdinando
F
D000818:Animals; D001943:Breast Neoplasms / Q000196:embryology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction
D011987:Receptors, Steroid; D000242:Cyclic AMP