Venables R S, McLean S, Luny D, Moteleb E, Morley S, Quinlan R A, Lane E B, Hutchison C J
Department of Biological Sciences, University of Dundee, UK.
Br J Cancer. 2001 Feb;84(4):512-9. doi: 10.1054/bjoc.2000.1632.
In this study we used a unique collection of type specific anti-lamin antibodies to study lamin expression patterns in normal human skin and in skin derived from patients with basal cell carcinomas (BCCs). Lamin expression in serial sections from frozen tissue samples was investigated by single and double indirect immunofluorescence. In normal skin, lamin A was expressed in dermal fibroblasts and in suprabasal epithelial cells but was absent from all basal epithelial cells. Lamin C was expressed in dermal fibroblasts, suprabasal epithelial cells and a majority of basal epithelial cells. However, lamin C was not expressed in quiescent basal epithelial cells. Lamin B1 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B2 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B2 was expressed in all cell types in normal skin. Lamin expression was also investigated in a collection of 16 BCCs taken from a variety of body sites. Based upon patterns of lamin expression the BCCs were classified into four groups: A-negative (10/16 tumours), C-negative (5/16 tumours), A/C-negative (1/16 tumours) and A/B2-negative (1/16 tumours). Lamin expression was also compared to cell proliferation index by staining serial sections with the proliferation marker Ki67. 9/10 of the lamin A negative tumours were highly proliferative, whereas 4/5 of the lamin C negative tumours were slow growing. Thus as a general rule absence of lamin A was correlated with rapid growth within the tumour, while absence of lamin C was correlated with slow growth within the tumour. Our data supports the hypothesis that lamin A has a negative influence on cell proliferation and its down regulation may be a requisite of tumour progression.
在本研究中,我们使用了一组独特的、针对特定核纤层蛋白的抗体来研究正常人皮肤以及基底细胞癌(BCC)患者皮肤中的核纤层蛋白表达模式。通过单重和双重间接免疫荧光法研究了来自冷冻组织样本的连续切片中的核纤层蛋白表达情况。在正常皮肤中,核纤层蛋白A在真皮成纤维细胞和基底上层上皮细胞中表达,但在所有基底上皮细胞中均未表达。核纤层蛋白C在真皮成纤维细胞、基底上层上皮细胞以及大多数基底上皮细胞中表达。然而,核纤层蛋白C在静止的基底上皮细胞中不表达。核纤层蛋白B1在所有上皮细胞中表达,但在真皮成纤维细胞中不表达。最后,核纤层蛋白B2在所有上皮细胞中表达,但在真皮成纤维细胞中不表达。最后,核纤层蛋白B2在正常皮肤的所有细胞类型中均有表达。我们还研究了从身体不同部位采集的16例基底细胞癌中的核纤层蛋白表达情况。根据核纤层蛋白的表达模式,将基底细胞癌分为四组:A阴性(10/16肿瘤)、C阴性(5/16肿瘤)、A/C阴性(1/16肿瘤)和A/B2阴性(1/16肿瘤)。还通过用增殖标记物Ki67对连续切片进行染色,将核纤层蛋白表达与细胞增殖指数进行了比较。10例核纤层蛋白A阴性肿瘤中有9例具有高增殖性,而5例核纤层蛋白C阴性肿瘤中有4例生长缓慢。因此,一般来说,核纤层蛋白A的缺失与肿瘤内的快速生长相关,而核纤层蛋白C的缺失与肿瘤内的缓慢生长相关。我们的数据支持这样的假设,即核纤层蛋白A对细胞增殖有负面影响,其下调可能是肿瘤进展的必要条件。