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Previously, we have shown that constitutively active Ack1 (caAck1) directly binds and tyrosine phosphorylates the androgen receptor (AR), resulting in ligand-independent AR activity. Moreover, caAck1 transforms LNCaP cells into androgen independent and highly invasive tumors in nude mice. However, the role of Ack1 in prostate cancer initiation and progression within the context of a complex organ remains poorly understood. To address this question, we generated transgenic mice expressing the caAck1 transgene throughout the prostate epithelium, driven by a modified rat probasin promoter. PbAck1 mice were then crossed to genetically engineered mice (Pten+/-and TgAP-T121) which develop murine prostate intraepithelial neoplasias (mPIN) or adenocarcinoma. PbAck1 prostates presented focal hyperplasia and nuclear atypia as early as 16 weeks of age. These prostatic lesions progressed to mPIN as detected in prostates from 49 weeks old PbAck1 mice. Crossing of PbAck1 mice to TgAPT121 mice resulted in accelerated onset of adenocarcinoma which was detected as early as 24 weeks of age. Furthermore, the apoptotic index was reduced by 50% in bi-transgenic prostates when compared to single TgAPT121 prostates. An increase in serine-phospho-p65 was also observed in the bi-transgenic when compared to the TgAPT121 prostates. PbAck1;Pten+/- compound mice presented mPIN lesions as early as 16 weeks of age; a 20 week acceleration. Increased Ki67 and phospho-serine Akt immunostaining correlated with loss of PTEN immunostaining, suggesting PTEN loss of heterozygosity. In summary, these data present evidence that Ack-1's oncogenic activity can promote the initiation and progression of prostate cancer in vivo.

The Military Educators Resource Network (MERN) is a part of the Basic Skills Resource Center which provides military educators with information on basic skills and continuing education. This design plan (1) synthesizes the result of a needs assessment; (2) provides an overview of planning considerations for the MERN information center; and (3) details the resources needed to develop the MERN document collection and database. Keywords: Adult education; Army continuing education system; Army education information system; Computer-based information systems; Computer applications; Information centers; Information systems; Technical information centers.