Gillenwater A, Xu X C, Estrov Y, Sacks P G, Lotan D, Lotan R
Department of Tumor Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Int J Cancer. 1998 Jan 19;75(2):217-24. doi: 10.1002/(sici)1097-0215(19980119)75:2<217::aid-ijc9>3.0.co;2-x.
Galectin-1 and galectin-3 are beta-galactoside-binding proteins thought to be important for cellular interactions, growth regulation and differentiation. Alterations in cellular content of galectins have been associated with differentiation, transformation and malignant progression. We examined the modulation of galectin-1 and galectin-3 expression in head and neck squamous cell carcinoma (HNSCC) cell lines by treatment with sodium butyrate, a known differentiation-modulating agent, and identified potential mechanisms of butyrate regulation of galectin-1 levels in one of the cell lines. Sodium butyrate effected an increase in galectin-1 protein concentration in 5 of 8 cell lines. One cell line, MDA-886LN, showed a marked time- and dose-dependent increase from barely detectable amounts with butyrate treatment. Concurrently with increased galectin-1 expression, butyrate treatment promoted morphologic changes, induced growth inhibition and inhibited soft agar colony formation in MDA-886LN cells. Butyrate-treated MDA-886LN cells demonstrated increased galectin-1 mRNA content, suggesting a role for butyrate in transcriptional regulation of galectin-1 expression. Treatment with other inhibitors of histone deacetylase also induced an increase in galectin-1 expression. Together, our results indicate that butyrate treatment can modulate galectin-1 content in MDA-886LN HNSCC cells as well as induce morphologic changes and growth inhibition. This action may involve a combination of transcriptional regulation and inhibition of histone deacetylation.
半乳糖凝集素-1和半乳糖凝集素-3是β-半乳糖苷结合蛋白,被认为对细胞间相互作用、生长调节和分化很重要。半乳糖凝集素细胞含量的改变与分化、转化和恶性进展有关。我们用已知的分化调节剂丁酸钠处理头颈部鳞状细胞癌(HNSCC)细胞系,检测半乳糖凝集素-1和半乳糖凝集素-3表达的调节情况,并在其中一个细胞系中确定了丁酸钠调节半乳糖凝集素-1水平的潜在机制。丁酸钠使8个细胞系中的5个细胞系半乳糖凝集素-1蛋白浓度增加。一个细胞系MDA-886LN在丁酸钠处理后,从几乎检测不到的水平呈现出明显的时间和剂量依赖性增加。在半乳糖凝集素-1表达增加的同时,丁酸钠处理促进了MDA-886LN细胞的形态变化,诱导了生长抑制并抑制了软琼脂集落形成。丁酸钠处理的MDA-886LN细胞显示半乳糖凝集素-1 mRNA含量增加,表明丁酸钠在半乳糖凝集素-1表达的转录调节中起作用。用其他组蛋白脱乙酰酶抑制剂处理也诱导了半乳糖凝集素-1表达增加。总之,我们的结果表明,丁酸钠处理可以调节MDA-886LN HNSCC细胞中的半乳糖凝集素-1含量,并诱导形态变化和生长抑制。这种作用可能涉及转录调节和组蛋白脱乙酰化抑制的联合作用。