Elevated expression and activation of the focal adhesion kinase (FAK) occurs in a large proportion of human breast cancers. Although several studies have implicated FAK as an important signaling molecule in cell culture systems, evidence supporting a role for FAK in mammary tumor progression is lacking. To directly assess the role of FAK in this process, we have used the Cre/loxP recombination system to disrupt FAK function in the mammary epithelium of a transgenic model of breast cancer. Using this approach, we demonstrate that FAK expression is required for the transition of premalignant hyperplasias to carcinomas and their subsequent metastases. This dramatic block in tumor progression was further correlated with impaired mammary epithelial proliferation. These observations provide direct evidence that FAK plays a critical role in mammary tumor progression.breast cancer ͉ Cre recombinase ͉ transgenic C ross-talk between integrin receptors and activated growth factor receptors has been hypothesized to play a critical role in the initiation and progression of cancer (1). Numerous in vitro studies have documented the importance of integrin receptors and their associated signaling molecules, including integrin-linked kinase (ILK), focal adhesion kinase (FAK), and the Src family of tyrosine kinases, in the regulation of cancer cell proliferation (2-4). In this regard, using the Cre/loxP recombination system, we have demonstrated that mammary epithelial ablation of ␤1-integrin severely impaired tumor initiation in the polyomavirus middle T (PyVmT) transgenic mouse model of breast cancer (5). Moreover, the ablation of ␤1-integrin expression in established primary mammary tumor cells was associated with a dramatic block in cell proliferation (5). Interestingly, molecular and biochemical analyses of the ␤1-integrin-null mammary tumor cells revealed that the block of cancer cell proliferation was associated with a dramatic decrease in FAK tyrosine phosphorylation (5). FAK is one of the major components of focal adhesion complexes. It regulates integrin-mediated cell adhesion and migration and is involved in the control of cell proliferation and survival (6-8). In a normal physiological context, engagement of integrin receptors by extracellular matrix proteins results in the rapid activation of Src and tyrosine phosphorylation of FAK (3, 4). FAK, in turn, phosphorylates downstream substrates, such as paxillin, on tyrosine residues and facilitates the recruitment of scaffold proteins like p130Cas (6).Several reports have shown that FAK is overexpressed in different types of cancer, with its levels of expression often associated with advanced disease (7, 9). In vivo, the importance of FAK in tumorigenesis was established in a study in which fak was selectively deleted in the epidermis. This conditional ablation of FAK resulted in the complete block in the progression of benign papilloma lesions to malignant carcinomas in a skin carcinogenesis model (10). There is an increasing body of evidence implicating FAK activation i...

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Somatostatin is a neuropeptide family that is produced by neuroendocrine, inflammatory, and immune cells in response to different stimuli. Somatostatin acts as an endogenous inhibitory regulator of various cellular functions including secretions, motility, and proliferation. Its action is mediated by a family of G-protein-coupled receptors (called sst1-sst5) that are widely distributed in the brain and periphery. The five receptors bind the natural peptides with high affinity, but only sst2, sst5, and sst3 bind the short synthetic analogs used to treat acromegaly and neuroendocrine tumors. This review covers the current knowledge in somatostatin receptor biology and signaling.