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Metallothionein Promotes Laminin-1-induced Acinar Differentiation in Vitro and Reduces Tumor Growth in Vivo¹

National Institute of Dental and Craniofacial Research, Center for Information Technology [V. V. P., P. J. M.] and Cell Biology [D. H., D. J., M. P. H., H. K. K.], NIH, Bethesda, Maryland 20892

Laminin-1 was found previously to promote the morphological differentiation of a salivary gland cell line (HSG) into acinar-like structures with polarized nuclei (1) . Here, microarray analysis showed that laminin-1 induced mainly one gene family of proteins, the metal binding metallothioneins (MTs), out of more than 10,500 cDNAs screened. Northern and protein analyses demonstrated that MT was increased some 5–10-fold by laminin-1 as early as 6 h after incubation. Cells transfected with this gene formed 3–5-fold larger acinar-like structures on exposure to laminin-1 in vitro and smaller, more differentiated tumors in vivo. We conclude that MTs are important in acinar cell morphological differentiation and may have novel functions other than metal binding.

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