Metallothionein promotes laminin-1-induced acinar differentiation in vitro and reduces tumor growth in vivo.

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.