Identifying Metastasis-Suppressor Genes in Cancer

描述（由申请人提供）：大约25%的前列腺癌男性在远离前列腺的位置发生肿瘤。前列腺癌死亡率与肿瘤转移性疾病的发展密切相关。临床结果表明在转移的继发部位存在显著的生长控制或转移抑制机制。因此，了解使肿瘤细胞易于发生转移的细胞和分子事件至关重要。 在这项研究计划中，我们计划使用在小鼠中开发的转移性前列腺癌实验模型。该模型使我们能够研究前列腺癌细胞发生转移的趋势。我们预测，转移的趋势可以解释为一个小的细胞亚群，已获得一个新的遗传缺陷。我们已经获得了实验小鼠前列腺肿瘤细胞，这些细胞要么发生转移，要么保持局部化。我们计划比较转移性细胞与非转移性细胞中基因的表达模式。然后，我们将这些基因表达模式与细胞中的基因组缺陷相关联。该项目的最终目标是确定在正常情况下可能阻止转移，但在发生某些遗传缺陷时促进转移的基因子集。一旦候选的转移抑制基因被鉴定，它们在生物学测定中抑制转移的能力将被证实。 这些实验的结果将为前列腺癌转移所需的基因提供新的信息。这些发现将提高医生对这些患者的诊断和预后能力，并导致新的治疗靶点，以防止前列腺癌的转移性扩散。 拟议的实验将为候选人提供癌症生物学的新培训，并进一步成熟生物信息学。预计他在K01奖期间的成就将有助于候选人在未来成为独立研究人员。

DESCRIPTION (provided by applicant): Approximately 25% of men with prostate cancer develop tumor at locations remote from the prostate gland. Prostate cancer mortality is strongly correlated with the development of tumor metastatic disease. Clinical findings indicate existence of significant growth control or metastasis inhibition mechanisms at secondary sites of metastases. Therefore, it is critical to understand the cellular and molecular events that predispose tumor cells to undergo metastasis. In this research proposal, we plan to use an experimental model of metastatic prostate cancer developed in mice. This model allows us to study the tendency of prostate cancer cells to undergo metastasis. We predict that the tendency for metastasis can be explained by a small subpopulation of cells that have acquired a new genetic defect. We have access to experimental mouse prostate tumor cells that either undergo metastasis or remain localized. We plan to compare the expression patterns of genes in metastatic cells with those of non-metastatic cells. We will then correlate these patterns of gene expression with genomic defects in the cells. The ultimate goal of this project is to identify a subset of genes that may prevent metastasis under normal conditions, but promote metastasis when certain genetic defects occur. Once candidate metastasis-suppressor genes have been identified, their ability to suppress metastasis in a biological assay will be confirmed. Results from these experiments will provide new information on genes required for the metastasis of prostate cancer. These findings will improve diagnostic and prognostic abilities of physicians caring for these patients as well as leading to new therapeutic targets to prevent metastatic spread of prostate cancer. The proposed experiments will provide the candidate with new training in cancer biology, and further maturation in bioinformatics. It is expected that his accomplishments during this K01 award period will help the candidate become an independent research in the future.