The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression.
LAPTM4b (lysosome associated protein transmembrane 4 beta) was recently identified as a gene overexpressed in human hepatocellular carcinoma and belongs to the mammalian LAPTM family. By analysing genome-wide expression profiles of microdissected solid tumour samples by the means of Affymetrix GenChip hybridisation, we found LAPTM4b to be upregulated in 88% (23/26) of lung and in 67% (18/27) of colon carcinoma patients. Northern blots revealed additionally an overexpression of LAPTM4b in the majority of carcinomas of the uterus (30/44), breast (27/53) and ovary (11/16). Other members of the LAPTM family were not overexpressed in the investigated tumour samples according to GeneChip hybridisation data. Northen blot and quantitative RT-PCR on different normal tissues, detected highest levels of LAPTM4b mRNA in uterus, heart and skeletal muscle. Due to sequence analysis of bilaterian LAPTM proteins we suggests the presence of four transmembrane helices per protein, which are probably packed together by hydrophobic forces that are excerted by several evolutionary conserved aromatic residues within the alpha-helices. We discuss an active role for LAPTM4b during disease progression of malignant cells and conclude that its putative dual functional involvement in tumour cell proliferation as well as in multidrug-resistance may represent LAPTM4b as a target suitable for development of novel therapeutic agents.
Kasper
Grit
G
metaGen Pharmaceuticals GmbH i.L., Oudenarderstr. 16, 13347 Berlin, Germany.
Vogel
Anke
A
Klaman
Irina
I
Gröne
Jörn
J
Petersen
Iver
I
Weber
Birgit
B
Castaños-Vélez
Esmeralda
E
Staub
Eike
E
Mennerich
Detlev
D
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D018432:Drug Resistance, Multiple; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D015854:Up-Regulation
C477083:LAPTM4B protein, human; D008565:Membrane Proteins; D015513:Oncogene Proteins