title: Laminin-5 beta3A expression in LNCaP human prostate carcinoma cells increases cell migration and tumorigenicity.
abstract: Interactions between extracellular matrix proteins and prostate carcinoma cells change dramatically during prostate tumor progression. We have concentrated on two key modifications that occur in the hemidesmosome in prostate carcinoma: loss of laminin-5 protein expression and altered basal cell polarity of the alpha6beta4 integrin. We previously demonstrated two cell line-specific isoforms (beta3A and beta3B) of the LAMB3 message. Cells expressing only the beta3B isoform did not translate the beta3 protein and were unable to assemble the laminin-5 trimer. One such cell line, LNCaP, was selected to determine whether restoration of the laminin-5 beta3A isoform would cause expression of a functional laminin-5 beta3 chain, assembly and secretion of the laminin-5 trimer, and reversion to a non-neoplastic phenotype. Laminin-5 beta3A cDNA was cloned and stably transfected into LNCaP cells. We observed the restoration of the beta3 protein, but a laminin-5 trimer was not secreted. Moreover, increased cell migration was demonstrated, and tumorigenicity was increased in SCID mice. A microarray analysis, performed between transfected and nontransfected LNCaP cells, showed most changing genes to be associated with signal transduction. The beta3 chain of laminin-5 may thus play an important role in signal transduction, which may enhance cell motility and tumorigenesis.
authors.affiliation: Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson, AZ, USA. rcalaluce@azcc.arizona.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Calaluce
authors.forename: David J
authors.initials: DJ
authors.lastname: Bearss
authors.forename: Jean
authors.initials: J
authors.lastname: Barrera
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Haiyong
authors.initials: H
authors.lastname: Han
authors.forename: Shaleen K
authors.initials: SK
authors.lastname: Beck
authors.forename: Kathy
authors.initials: K
authors.lastname: McDaniel
authors.forename: Ray B
authors.initials: RB
authors.lastname: Nagle
mesh_terms: D000818:Animals; D001681:Biological Assay; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement; D020869:Gene Expression Profiling; D006801:Humans; D039503:Integrin alpha6 / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D039503:Integrin alpha6; D020033:Protein Isoforms; D000097794:Kalinin