Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, Iowa, USA.
Prostate. 2010 May 15;70(7):777-87. doi: 10.1002/pros.21110.
Dystroglycan is a cell-surface receptor for extracellular matrix proteins including laminins and perlecan. Prior studies have shown its involvement in assembly and/or maintenance of basement membrane structures, cell polarity and tissue morphogenesis; and its expression is often reduced in prostate and other cancers. However, the role of dystroglycan in normal epithelial tissues such as the prostate is unclear.
To investigate this, we disrupted dystroglycan expression in the prostate via a conditional gene targeting strategy utilizing Cre recombinase expressed in luminal prostate epithelial cells.
Contrary to expectations, deletion of dystroglycan in luminal epithelial cells resulted in no discernable phenotype as judged by histology, basement membrane ultrastructure, localization of dystroglycan ligands, cell polarity or regenerative capacity of the prostate following castration. Dystroglycan expression remains in keratin-5-positive basal cells located in the proximal ducts where dystroglycan expression is elevated in regenerating prostates.
Our results show that dystroglycan in luminal epithelial cells is not required for the maintenance of basement membranes, cell polarity or prostate regeneration. However, it is possible that persistent dystroglycan expression in the basal cell compartment may support these or other functions.
层粘连蛋白和 Perlecan 等细胞外基质蛋白的细胞表面受体是 dystroglycan。先前的研究表明它参与了基底膜结构、细胞极性和组织形态发生的组装和/或维持;其表达在前列腺癌和其他癌症中常常降低。然而,dystroglycan 在前列腺等正常上皮组织中的作用尚不清楚。
为了研究这一点,我们利用在腔上皮细胞中表达的 Cre 重组酶,通过条件性基因靶向策略破坏前列腺中的 dystroglycan 表达。
出乎意料的是,腔上皮细胞中 dystroglycan 的缺失并没有导致组织学、基底膜超微结构、dystroglycan 配体的定位、细胞极性或去势后前列腺的再生能力的可察觉表型。dystroglycan 的表达仍然存在于位于近端导管中的角蛋白 5 阳性基底细胞中,在再生的前列腺中,dystroglycan 的表达升高。
我们的结果表明,腔上皮细胞中的 dystroglycan 对于维持基底膜、细胞极性或前列腺再生不是必需的。然而,基底细胞隔室中持续的 dystroglycan 表达可能支持这些或其他功能。