Slade M J, Coope R C, Gomm J J, Coombes R C
Department of Cancer Medicine, Imperial College School of Medicine, Charing Cross Campus, St. Dunstan's Road, London, W6 8RP, England.
Exp Cell Res. 1999 Feb 25;247(1):267-78. doi: 10.1006/excr.1998.4340.
We show that myoepithelial cell basement membrane derived E3 and E8 domains of laminin-1 are capable of polarizing luminal epithelial cells with regard to epithelial membrane antigen localization. This event is dependent on the alpha6 integrin and results in aggregation and phosphorylation of the tyrosine residues of the focal adhesion kinase complex. We also demonstrate that uncultured normal luminal epithelial cells synthesize normal levels of beta and gamma laminin chains and reduced levels of alpha chains mRNA in common with malignant epithelial cells. In contrast normal myoepithelial cells synthesize all three constituent chains of laminin-1. Therefore in breast cancer the absence of myoepithelial cells could result in a lack of laminin alpha chains which may contribute to loss of polarity of malignant epithelial cells.
我们发现,层粘连蛋白-1的肌上皮细胞基底膜衍生的E3和E8结构域能够使管腔上皮细胞在上皮膜抗原定位方面发生极化。这一事件依赖于α6整合素,并导致粘着斑激酶复合物酪氨酸残基的聚集和磷酸化。我们还证明,未培养的正常管腔上皮细胞与恶性上皮细胞一样,合成正常水平的β和γ层粘连蛋白链,而α链mRNA水平降低。相比之下,正常肌上皮细胞合成层粘连蛋白-1的所有三条组成链。因此,在乳腺癌中,肌上皮细胞的缺失可能导致层粘连蛋白α链的缺乏,这可能导致恶性上皮细胞极性的丧失。