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),...

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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
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Summary: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.
ISSN:0008-5472
1538-7445