Expression of individual lamins in basal cell carcinomas of the skin

Abstract

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 B 1 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B 2 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B 2 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/B 2 -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. © 2001 Cancer Research Campaign http://www.bjcancer.com

Cell-cycle-dependent dynamics of nuclear pores: pore-free islands and lamins

“…In good agreement with our observations, embryonic cells whose nuclei lack A-type lamins have a much higher nuclear pore density (40-50 NPCs/m 2 ) and proliferation activity (Maul et al, 1980). Furthermore, several studies have reported that the absence or downregulation of lamin A/C is correlated with rapid growth or aggressivity in human malignancies including small-cell lung carcinoma (Broers and Ramaekers, 1994), testicular cancer (Machiels et al, 1997), leukemias and lymphomas (Stadelmann et al, 1990) and skin carcinomas (Venables et al, 2001). These reports support the hypothesis that lamin A/C has a negative influence on cell proliferation.…”

Nuclear lamins: key regulators of nuclear structure and activities

“…Reduced or null expression of lamins A and C in basal cell carcinomas (BCC) was correlated with a rapid growth rate within the tumour, whereas absence of lamin C only was correlated with a slow growth rate within the tumour [189,190]. In contrast, another study has found the presence of significant amounts of lamins A and C in proliferating BCC cells [191].…”

Remodelling of the nuclear lamina and nucleoskeleton is required for skeletal muscle differentiation in vitro

“…For immunoblotting, proteins separated on 10% gels were electrophoretically transferred to nitrocellulose (0.2 mm; Schleicher and Schuell) in 48 mM Tris-HCl, pH 9.4, 39 mM glycine by using the Mini Transblot system (Bio-Rad). Primary antibodies were used as follows: anti-myogenin, rabbit polyclonal, 1:500, Santa Cruz Biotechnology; Jol4, anti-lamin-A, mouse monoclonal, 1:10 (Dyer et al, 1997); C-20, anti-lamin-B1, goat polyclonal, 1:500, Santa Cruz Biotechnolgy; anti-lamin-C, rabbit polyclonal, 1:500 (Venables et al, 2001); LN43, anti-lamin-B2, mouse monoclonal, 1:10 (Venables et al, 2001); LAP15, anti-LAP2α mouse monoclonal, 1:10 (Dechat et al, 2000); anti-RbS780, 1:1000, Cell Signalling. Secondary antibodies were donkey anti-mouse, donkey anti-rabbit or donkey anti-goat IgG conjugated to horseradish peroxidase (Jackson Immunoresearch).…”