The FGF signaling axis in prostate tumorigenesis

The prostate and prostate cancer The prostate is an acorn-shaped accessory gland of the male reproductive system that secretes a variety of products into semen. Human prostate has three distinct zones: the peripheral zone, the transition zone, and the central zone. In Western societies, prostate cancer is the most frequently diagnosed neoplasm in males and the second leading cause of cancer mortality (1). About 5, 10, and 85% of human prostate cancer cases originate from the central zone, transition zone, and peripheral zone, respectively (1). Early prostate lesions are organ-confined, androgen-responsive, and are often alleviated by surgery (2). Over time and progression to advanced stages, however, the lesions frequently metastasize to bones, lymph nodes, and other organs, and usually become androgen-insensitive and lethal. To date, there is still no effective therapy for advanced prostate cancer. Understanding the mechanisms underlying the onset, progression to malignancy, and metastasis of prostate cancer is needed for developing new diagnostic, preventive, and therapeutic approaches. The progression of prostate cancer is a slow and multi-step process. Although prostate cancer originates as focal lesions at early ages, clinically detectable prostate cancers are usually manifested in men after age 60. Animal models that mimic human prostate cancer initiation, progression, and metastasis are needed to understand the etiology and development of prostate cancer, and to test new prevention and intervention strategies for prostate cancer. Rodents have a strikingly different prostate morphology than humans and seldom develop spontaneous prostate tumors. Rare spontaneous and induced transplantable tumors from rats such as the Dunning tumor model that recapitulates some aspects of human prostate cancer progression in respect to stroma and epithelial compartments has been widely productive in understanding the general mechanisms underlying prostate tumor progression and castration resistance (3). However, the infrequent spontaneity of tumors in rodents and limitations in genetic manipulation of rats has made genetic manipulation in mice the avenue for developing new prostate tumor models. The mouse prostate consists of four distinct pairs of lobes: the anterior lobes (AP, also known as the coagulating gland), dorsal lobes (DP), lateral lobes (LP), and ventral lobe (VP; 4,5). The dorsal and lateral lobes are often referred to as the dorsolateral lobe (DLP). Despite the difference in organ morphology, both human and mouse prostates are composed of a complex ductal network that has general epithelial and stromal compartments comprised of diverse subcellular types within each (6).