title: Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations.
abstract: Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies "initial" and "final" passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations.
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Becerikli
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jacobsen
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rittig
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Köhne
authors.affiliation: Institute of Pathology, Ruhr-University Bochum, Germany.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Nambiar
authors.affiliation: Institute of Pathology, Ruhr-University Bochum, Germany.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mirmohammadsadegh
authors.affiliation: Institute of Pathology, Ruhr-University Bochum, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Stricker
authors.affiliation: Institute of Pathology, Ruhr-University Bochum, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieczorek
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Germany.
authors.forename: Joerg Thomas
authors.initials: JT
authors.lastname: Epplen
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tilkorn
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany. Electronic address: lars.steinstraesser@rub.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Steinstraesser
mesh_terms: D059786:Abnormal Karyotype; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D020868:Gene Silencing; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins