Characterization of the human laminin β2 chain locus (LAMB2): linkage to a gene containing a nonprocessed, transcribed LAMB2-like pseudogene (LAMB2L) and to the gene encoding glutaminyl tRNA synthetase (QARS)

Durkin, Marian E.; Jäger, Anne Charlotte; Khurana, T.S.; Nielsen, Finn C.; Albrechtsen, Reidar; Wewer, Ulla M.

doi:10.1159/000015249

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…[30][31][32] Changes in the levels of the laminin β2 chain have been found in pathological conditions such as cancer, diabetes, and neuromuscular disorders. [33][34][35][36] The cell adhesion to type IV collagen does not require any laminins. This cell adhesion is known as mediated by integrin a1 β1 or a2β1, while laminins bind cells through other integrins such as a6β1 and a3β1.…”

Section: Discussionmentioning

confidence: 99%

Elevated Cell Invasion Is Induced by Hypoxia in a Human Pituitary Adenoma Cell Line

Yoshida

Teramoto

2007

Cell Adhesion & Migration

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Pituitary adenoma tissues are hypovascular, and have a lower partial oxygen pressure compared with neighboring normal organs. In this study, we investigated whether hypoxia influences the cell invasiveness of the human pituitary adenoma cell line, HP-75. HP-75 cells were exposed to hypoxic (1-10% oxygen) or normoxic (21% oxygen) conditions for 24 hours. Gelatin and reverse zymogram assays were used to determine the enzyme activities of matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP). Cell adhesion and Matrigel cell invasion were examined with a Boiden chamber. Finally, the mRNA gene expression profiles of cells exposed to hypoxia or normoxia were examined by cDNA microarray and confirmed with real-time RT-PCR and flow cytometry. The gelatin and reverse zymograms revealed that the activities of MMP and TIMP were not significantly altered by hypoxia. Matrigel cell invasion and cell adhesion to Matrigel or collagen type IV were increased by hypoxia (3.8-and 4.8-fold, respectively). The cDNA microarray analysis revealed that laminin β2 chain mRNA was specifically up-regulated under hypoxic conditions (4.96-fold). Finally, real-time RT-PCR and flow cytometry verified the elevated expression of laminin β2 chain at the mRNA and protein levels under hypoxic conditions. RNA interference with siRNA targeting laminin β2 inhibited Matrigel invasion and adhesion to collagen type IV in a dose-dependent manner.Collectively, these results suggested that hypoxia (1% oxygen) enhanced the cell invasion properties of a pituitary adenoma cell line in association with elevated expression of laminin β2 and enhanced binding to collagen type IV.

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Section: Discussionmentioning

confidence: 99%

Elevated Cell Invasion Is Induced by Hypoxia in a Human Pituitary Adenoma Cell Line

Yoshida

Teramoto

2007

Cell Adhesion & Migration

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“…The other candidate was the predicted gene ENSDARG00000033950, which encoded a protein 49% identical to lamb2. This second gene, lamb2l, was situated in the same relative location as human LAMB2-like, a pseudogene, which is adjacent and upstream of LAMB2 (Durkin et al, 1999). The gene order in this region is conserved between human and zebrafish ( Fig.…”

Section: The Vertical Myoseptum In Sof Mutants Has An Abnormal Ultrasmentioning

confidence: 92%

The zebrafish dystrophic mutantsoftymaintains muscle fibre viability despite basement membrane rupture and muscle detachment

et al. 2009

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The skeletal muscle basement membrane fulfils several crucial functions during development and in the mature myotome and defects in its composition underlie certain forms of muscular dystrophy. A major component of this extracellular structure is the laminin polymer, which assembles into a resilient meshwork that protects the sarcolemma during contraction. Here we describe a zebrafish mutant, softy, which displays severe embryonic muscle degeneration as a result of initial basement membrane failure. The softy phenotype is caused by a mutation in the lamb2 gene, identifying laminin β2 as an essential component of this basement membrane. Uniquely, softy homozygotes are able to recover and survive to adulthood despite the loss of myofibre adhesion. We identify the formation of ectopic, stable basement membrane attachments as a novel means by which detached fibres are able to maintain viability. This demonstration of a muscular dystrophy model possessing innate fibre viability following muscle detachment suggests basement membrane augmentation as a therapeutic strategy to inhibit myofibre loss.

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“…3). Downstream of the last exon of the β2 chain gene is another GC‐rich region typical of a CpG island [30]. A 1.1‐kb Xho I/ Sac I fragment containing the CpG island was subcloned downstream of the luciferase gene in p(−667/+297)luc, and transiently transfected into both cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously determined the exon–intron organization of the 12‐kb human laminin β2 chain gene and characterized the surrounding genomic DNA on chromosome 3p21.3 [8,30]. In this report, we have studied the control of laminin β2 chain gene expression at both the transcriptional and post‐transcriptional level in human cancer cell lines.…”

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confidence: 99%

Regulation of laminin β2 chain gene expression in human cancer cell lines

Durkin

Nielsen

Loechel

et al. 2001

European Journal of Biochemistry

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The laminin β2 chain is a basement membrane component expressed in a tissue‐ and developmental stage‐specific manner. In this report we have examined the transcriptional and post‐transcriptional regulation of the human laminin β2 chain in human tumor cell lines. Both the A204 rhabdomyosarcoma and clone A colon carcinoma cells express the laminin β2 chain mRNA, but only the A204 cells secrete laminin heterotrimers containing the β2 chain. Segments of the β2 chain gene promoter region were cloned into luciferase reporter vectors, and their ability to stimulate transcription was tested by transient transfection. Sequences downstream of the transcription start site between nucleotides +91 and +120 were found to be essential for luciferase activity in the two cell lines. Additional positive regulatory regions were present further upstream, between nucleotides −164 to −667 and between nucleotides −667 to −1724. Genomic DNA at the 3′ end of the gene also appeared to have enhancer activity, as a 1.1‐kb fragment located downstream of the last exon stimulated the luciferase activity of the nucleotides −667/+297 promoter segment ≈ threefold. Alternative splicing of the first intron of the human laminin β2 chain gene generates two isoforms of the 5′ untranslated region of the β2 chain mRNA. The translational efficiencies of the two laminin β2 chain leaders did not differ significantly, when assayed by polysome profile analysis of endogenous clone A cell β2 chain mRNA, transient transfection of chimeric β2 chain leader/luciferase expression plasmids in clone A cells, and translation of in vitro synthesized RNAs in rabbit reticulocyte lysates.

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Characterization of the human laminin β2 chain locus (LAMB2): linkage to a gene containing a nonprocessed, transcribed LAMB2-like pseudogene (LAMB2L) and to the gene encoding glutaminyl tRNA synthetase (QARS)

Cited by 5 publications

References 25 publications

Elevated Cell Invasion Is Induced by Hypoxia in a Human Pituitary Adenoma Cell Line

Elevated Cell Invasion Is Induced by Hypoxia in a Human Pituitary Adenoma Cell Line

The zebrafish dystrophic mutantsoftymaintains muscle fibre viability despite basement membrane rupture and muscle detachment

Regulation of laminin β2 chain gene expression in human cancer cell lines

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