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.
Hecht
Dalit
D
Center for Information Technology, National Institute of Dental and Craniofacial Research/NIH, 30 Convent Drive, Bethesda, MD 20892, USA.
Jung
Dale
D
Prabhu
Vinay V
VV
Munson
Peter J
PJ
Hoffman
Matthew P
MP
Kleinman
Hynda K
HK
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D007797:Laminin; C121346:laminin 1; D008668:Metallothionein