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

• Published in: Cancer research (Chicago, Ill.) Ill.), 2002-09, Vol.62 (18), p.5370-5374
• Main Authors: HECHT, Dalit, JUNG, Dale, PRABHU, Vinay V, MUNSON, Peter J, HOFFMAN, Matthew P, KLEINMAN, Hynda K
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation - drug effects; Humans; Laminin - pharmacology; Metallothionein - biosynthesis; Metallothionein - genetics; Metallothionein - physiology; Mice; Mice, Nude; Molecular and cellular biology; Neoplasms, Experimental - genetics; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Oligonucleotide Array Sequence Analysis; Salivary Glands - cytology; Salivary Glands - metabolism; Salivary Glands - physiology; Transfection; Xenograft Model Antitumor Assays
• ISSN: 0008-5472; 1538-7445

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.