Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes.
Adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the lung are morphologically distinguished in part by cyto-architectural features. However, little is known about the relative expression and distribution of cyto-architectural proteins among AC, SCC and ASC. Initial microarray analysis revealed significant differences in expression of two cyto-architectural genes in AC, SCC and ASC. Desmoplakin (DP) 1 and 2, which link desmosomes to intermediate filaments, was strongly expressed in SCC relative to AC and ASC. Cytokeratin 18 (CK18), an intermediate filament that is commonly linked to desmoplakin, was strongly expressed in AC and ASC relative to SCC. Western blot analysis demonstrated that AC and ASC had abundant CK18 protein, whereas CK18 was weakly detected in SCC. DP 1 and 2 are strongly expressed in SCC and minimally expressed in AC and ASC. However, the ratio of one to the other is the same in SCC and AC, but DP2 is lost in ASC. Microscopic analysis with fluorescence-labeled antibodies for CK18 and DP 1 and 2 revealed abundant membrane localization of DP and minimal perinuclear localization of CK18 in SCC. In contrast, in both AC and ASC, the CK18 protein was diffusely distributed within the cytoplasm, and DP showed both membranous and cytoplasmic localization. In conclusion, the data here shows that AC, SCC and ASC each have specific patterns of DP 1 and 2 and CK18 gene expression, protein content and biodistribution.
Young
Geoffrey D
GD
Department of Medicine, University of Alabama at Birmingham, and Birmingham VAMC, 701 South 19th Street, LHRB 339, 35294, USA.
Winokur
Thomas S
TS
Cerfolio
Robert J
RJ
Van Tine
Brian A
BA
Chow
Louise T
LT
Okoh
Victor
V
Garver
Robert I
RI
D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051180:Desmoplakins; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051180:Desmoplakins; D007633:Keratins