Identifying Metastasis-Suppressor Genes in Cancer

描述(申请人提供)：大约25%的前列腺癌患者在远离前列腺癌的部位发生肿瘤。前列腺癌死亡率与肿瘤转移性疾病的发生密切相关。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，了解导致肿瘤细胞发生转移的细胞和分子事件是至关重要的。 在这项研究方案中，我们计划使用在小鼠身上建立的转移性前列腺癌的实验模型。这个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，转移的倾向可以通过获得新的遗传缺陷的一小部分细胞来解释。我们可以获得实验性的小鼠前列腺癌细胞，这些细胞要么发生转移，要么保持定位。我们计划比较转移细胞和非转移细胞中基因的表达模式。然后，我们将把这些基因表达模式与细胞中的基因组缺陷联系起来。该项目的最终目标是确定在正常情况下可能防止转移，但在发生某些基因缺陷时促进转移的基因子集。一旦确定了候选转移抑制基因，它们在生物学检测中抑制转移的能力将得到证实。 这些实验的结果将提供前列腺癌转移所需基因的新信息。这些发现将提高护理这些患者的医生的诊断和预后能力，并导致防止前列腺癌转移扩散的新治疗目标。 拟议的实验将为候选人提供癌症生物学方面的新培训，并在生物信息学方面进一步成熟。期待他在本次K01颁奖期间取得的成绩，将有助于候选人未来成为一名独立研究人员。

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.