Disease relevance of LAMC2

• Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5) [1].
• Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa [2].
• In 74 breast tumors, methylation frequencies LAMA3, LAMB3, and LAMC2 were 44, 4, and 20%, respectively [3].
• The frequency of methylation of LN5-encoding genes in prostate cancers and nonmalignant prostate tissues, respectively, were: 44 and 12% for LAMA3 (P = 0.001); 18 and 6% for LAMB3; and 41 and 9% for LAMC2 (P = 0.001) [4].
• Mutations in the genes (LAMA3, LAMB3, and LAMC2) encoding the subunit polypeptides of the cutaneous basement membrane zone protein laminin 5 have been reported in different forms of junctional epidermolysis bullosa (JEB), an inherited blistering skin disease [5].

High impact information on LAMC2

• We have linked Herlitz's junctional epidermolysis bullosa (H-JEB) to the gene (LAMC2) encoding the gamma 2 subunit of nicein/kalinin, an isolaminin (laminin-5) expressed by basal keratinocytes [1].
• In four H-JEB kindreds, a maximum two-point lod score of 5.33 at theta = 0 was observed between a microsatellite near LAMC2 at 1q25-31 and the disease [1].
• Comparative immunoprecipitation studies of patient sera, P1E1, and GB3 monoclonal antibody show that epiligrin is identical to the antigen (i.e., BM600 or GB3 antigen) previously reported to be absent from the skin of patients with lethal junctional epidermolysis bullosa, an inherited subepidermal blistering disease [6].
• The gene for the laminin B2t chain (LAMB2T) was localized to chromosome 1q25-q31 in close proximity to the laminin B2 chain gene [7].
• The 140-kDa peptide contains an amino acid sequence homologous to that of the laminin B2t chain [8].

Biological context of LAMC2

• Human serum augmented gene expressions of LAMA3, LAMB3, and LAMC2 in human keratinocytes to almost the same extent, and this was associated with an increase of the laminin 5 protein content measured by a specific sandwich enzyme-linked immunosorbent assay [9].
• Methylation of LAMA3 and LAMB3 and the methylation index were correlated significantly with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas methylation of LAMC2 and methylation index were associated with shortened patient survival [10].
• Delineation of novel homozygous nonsense mutations in the LAMB3 and LAMC2 genes, with previous demonstrations of LAMA3 mutations, re-emphasizes the concept that stop codon mutations in both alleles of any of the three laminin 5 genes result in the severe H-JEB phenotype [11].
• The remaining alleles were subjected to mutation screening by PCR amplification of individual exons of LAMB3 and LAMC2, followed by heteroduplex analysis and nucleotide sequencing [12].
• Here, we describe a non-Herlitz junctional epidermolysis bullosa patient, compound heterozygote for two novel mutations affecting the LAMC2 gene [13].

Anatomical context of LAMC2

• Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2 [10].
• PURPOSE: Laminin-5 (LN5) is an essential component of the basement membrane (BM) and is composed of three chains that are the products of three distinct genes (LAMA3, LAMB3, and LAMC2) [4].
• Methylation frequencies of LAMA3, LAMB3, and LAMC2 genes in 20 breast cancer cell lines were 40, 5, and 15%, respectively [3].
• A 2.5 kb portion of the LAMC2 5' flanking region was equally responsive to PMA and hepatocyte growth factor (HGF), whereas it was less responsive to transforming growth factor beta1 [14].
• However, elements outside -5900 and +55 are needed for normal epithelium expression of the LAMC2 gene [15].

Associations of LAMC2 with chemical compounds

• Furthermore, we present evidence that implicates mutations in the kalinin/laminin 5 gamma 2 chain gene (LAMC2) in some forms of junctional EB [16].
• EB has been described in several species, like cattle, sheep, dogs, cats and horses where the mutation, a cytosine insertion in exon 10 of the LAMC2 gene, was very recently identified in Belgian horses as the mutation responsible for JEB [17].
• This bacterium, designated strain B2T, represents aerobic, gram-negative, colourless, non-motile, curved coccoids that form conglomerates covered by an extracellular polysaccharide matrix [18].
• Three of them were obtained with methanol (strains H1M, H3M, and B1M), three strains with triethylene glycol (strains H1T, B1T, and B2T) and one strain with a mixture of lactate, acetate and butyrate (strain H1-13) [19].
• In uninvolved, perilesional and early pre-blistered lesional BP skin the distribution of both the alpha 6 and beta 4 integrin subunits, BPA laminin, collagen types IV and VII and the BM600 antigen was identical to normal skin, i.e. a linear band in the BMZ [20].

Other interactions of LAMC2

• Collectively, five mutations appeared to be frequent in laminin-5 JEB patients: R635X, 29insC, E210K, W143X in LAMB3 and R95X in LAMC2 [21].
• Laminin-5 is a heterotrimer protein consisting of the alpha3, beta3, and gamma2 chains, and another unique component of laminin-5 is the gamma2 chain encoded by the LAMC2 gene [22].
• Expression and topography of integrins and basement membrane proteins in epidermal carcinomas: basal but not squamous cell carcinomas display loss of alpha 6 beta 4 and BM-600/nicein [23].
• The localization and sensitivity of basement membrane components (bullous pemphigoid antigen, BM 600/nicein, epiligrin, kalinin, laminin, collagens IV and VII (EBA antigen) and linkin) were determined after the DEJ was fractured by each method [24].
• RESULTS: Four genes were demonstrated to be consistently overexpressed in invasive cervical cancer biopsies; three novel genes not previously related to cervical cancer: MMP10, Lamc2 and Claudin 1 [25].

Analytical, diagnostic and therapeutic context of LAMC2

• For amplification of cDNA generated by RT-PCR, eight primer pairs covering overlapping segments of the entire coding sequence of LAMC2 mRNA were used [26].
• By using in situ hybridization, we also show that the cells of the JE express the LAMC2 gene of laminin-5 [27].
• BM 600/nicein, epiligrin and kalinin were not detected after treatment with trypsin [24].

References