Bromodeoxyuridine Induces Integrin Expression at Transcriptional (α₂ Subunit) and Post-Transcriptional (β₁ Subunit) Levels, and Alters the Adhesive Properties of Two Human Lung Tumour Cell Lines

Abstract

Integrins are a family of transmembrane glycoproteins that participate in a wide range of cellular events including proliferation, apoptosis and differentiation. Little is known about the mechanisms that control integrin subunit expression in epithelial cells, especially during lung cell differentiation. We have examined the effect of the differentiation-modulating agent, 5-bromo-2′-deoxyuridine (BrdU), on integrin expression in 2 human lung carcinoma cell lines, DLKP and A549. Treatment of both DLKP and A549 with 10 μM BrdU for 7 days resulted in increased expression of α₂ and β₁ integrin subunit protein expression. Northern blot and RT-PCR analyses revealed progressively increasing levels of the α₂ mRNA transcripts following BrdU treatment up to 21 days in both cell lines. However, no increase in β₁ integrin mRNA levels was observed in either cell, suggesting post-transcriptional regulation by BrdU. Treatment of HL-60, a leukaemic cell line, with BrdU up to 21 days resulted in no change in α₂ or β₁ integrin subunit levels at either protein or mRNA levels suggesting that the change seen in the lung cell lines may be epithelial cell lineage-specific. BrdU has also been found to alter the adhesive properties of A549 and DLKP cells. Treated cells were found to adhere significantly faster to collagen type IV and laminin compared to untreated cells. The results presented here suggest that DLKP (and A549) may be useful cellular models to investigate the role of the α₂ β₁ integrin in lung epithelial cell differentiation.

Key Words:

• Bromodeoxyuridine
• integrin
• lung
• differentiation
• extracellular matrix