Analysis of the PTCH1 signaling pathway in ovarian dermoids.
Dermoids belong to the group of developmental cysts and arise from germ cells. Studies on these tumors may therefore increase our understanding of normal germ cell development within different environments and cell lines derived from these lesions may also constitute an important vehicle for studying neoplasia and differentiation. Recently, we investigated the status of the PTCH1 locus in a large set of sporadic non-inflammatory, developmental cystic lesions. Our data showed allelic loss of microsatellite markers in close vicinity to the PTCH1 locus in both odontogenic keratocysts and dentigerous cysts as well as in ovarian dermoid cysts (ODC). In this study, we closely examined the status of the PTCH1 gene in ODCs. Although about 25% of cysts demonstrated LOH at the PTCH1 locus, no nonsense or missense mutations in the coding region of PTCH1 were detected in genomic DNA isolated from any of the ODCs examined by direct sequencing. Staining with PTCH1 and GLI1 antibodies showed that proteins were present in virtually all epithelial linings, with variable staining intensity not correlated with LOH and generally weaker for GLI1. However, cDNA microarray analysis performed on cell lines derived from ODCs did not show any significant alteration in the expression of the analyzed target genes of PTCH1 signaling in any of the cell lines examined, except for CyclinD1 (and several other genes generally not associated with PTCH1 signaling).
Levanat
Sonja
S
Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia. levanat@rudjer.irb.hr.
Kappler
Roland
R
Hemmerlein
Bernhard
B
Döring
Patrick
P
Musani
Vesna
V
Komar
Arijana
A
Oreskovic
Slavko
S
Pavelic
Bozidar
B
Hahn
Heidi
H
D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D003884:Dermoid Cyst / Q000503:physiopathology*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000503:physiopathology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
D008565:Membrane Proteins; D015513:Oncogene Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1