Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW 2010, Australia
Sci Rep. 2012;2:526. doi: 10.1038/srep00526. Epub 2012 Jul 24.
β1 integrin regulates the response of both normal and cancer cells to their local environment. Although mis-localised in prostate cancer, the role β1 integrin plays in prostate development and carcinogenesis remains unknown. To assess the role of β1 integrin in vivo, we conditionally deleted β1 integrin from prostate epithelium and subsequently crossed these mice to the TRAMP prostate carcinogenesis model. Deletion of β1 integrin following castration and subsequent androgen supplementation resulted in an expansion of the p63-positive basal cell population and decreased differentiation. Consistent with these findings, deletion of β1 integrin in TRAMP mice decreased animal survival, decreased retention of normal prostate morphology, increased the percentage of tissue with poorly differentiated carcinoma, and increased cell proliferation. This study demonstrates that β1 integrin regulates several aspects of normal prostate development and in contrast to its role in several other tissues, its loss is associated with increased rates of prostate tumour progression.
β1 整合素调节正常细胞和癌细胞对其局部环境的反应。尽管在前列腺癌中定位错误，但β1 整合素在前列腺发育和癌变中的作用尚不清楚。为了评估β1 整合素在体内的作用，我们条件性地从前列腺上皮细胞中删除β1 整合素，随后将这些小鼠与 TRAMP 前列腺癌发生模型杂交。去势后和随后雄激素补充时删除β1 整合素导致 p63 阳性基底细胞群的扩张和分化减少。与这些发现一致的是，在 TRAMP 小鼠中删除β1 整合素会降低动物存活率，降低正常前列腺形态的保留率，增加组织中分化不良癌的百分比，并增加细胞增殖。这项研究表明，β1 整合素调节正常前列腺发育的几个方面，与它在其他几种组织中的作用相反，其缺失与前列腺肿瘤进展的速度增加有关。
