title: Differential gene regulation under altered gravity conditions in follicular thyroid cancer cells: relationship between the extracellular matrix and the cytoskeleton.
abstract: Extracellular matrix proteins, adhesion molecules, and cytoskeletal proteins form a dynamic network interacting with signalling molecules as an adaptive response to altered gravity. An important issue is the exact differentiation between real microgravity responses of the cells or cellular reactions to hypergravity and/or vibrations. To determine the effects of real microgravity on human cells, we used four DLR parabolic flight campaigns and focused on the effects of short-term microgravity (22 s), hypergravity (1.8 g), and vibrations on ML-1 thyroid cancer cells. No signs of apoptosis or necrosis were detectable. Gene array analysis revealed 2,430 significantly changed transcripts. After 22 s microgravity, the F-actin and cytokeratin cytoskeleton was altered, and ACTB and KRT80 mRNAs were significantly upregulated after the first and thirty-first parabolas. The COL4A5 mRNA was downregulated under microgravity, whereas OPN and FN were significantly upregulated. Hypergravity and vibrations did not change ACTB, KRT-80 or COL4A5 mRNA. MTSS1 and LIMA1 mRNAs were downregulated/slightly upregulated under microgravity, upregulated in hypergravity and unchanged by vibrations. These data indicate that the graviresponse of ML-1 cells occurred very early, within the first few seconds. Downregulated MTSS1 and upregulated LIMA1 may be an adaptive mechanism of human cells for stabilizing the cytoskeleton under microgravity conditions.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ulbrich
authors.forename: Jessica
authors.initials: J
authors.lastname: Pietsch
authors.forename: Jirka
authors.initials: J
authors.lastname: Grosse
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.forename: Katrin
authors.initials: K
authors.lastname: Saar
authors.forename: Norbert
authors.initials: N
authors.lastname: Hübner
authors.forename: Jens
authors.initials: J
authors.lastname: Hauslage
authors.forename: Ruth
authors.initials: R
authors.lastname: Hemmersbach
authors.forename: Markus
authors.initials: M
authors.lastname: Braun
authors.forename: Jack
authors.initials: J
authors.lastname: van Loon
authors.forename: Nicole
authors.initials: N
authors.lastname: Vagt
authors.forename: Marcel
authors.initials: M
authors.lastname: Egli
authors.forename: Peter
authors.initials: P
authors.lastname: Richter
authors.forename: Ralf
authors.initials: R
authors.lastname: Einspanier
authors.forename: Soroush
authors.initials: S
authors.lastname: Sharbati
authors.forename: Theo
authors.initials: T
authors.lastname: Baltz
authors.forename: Manfred
authors.initials: M
authors.lastname: Infanger
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D018263:Adenocarcinoma, Follicular; D002460:Cell Line; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018470:Gravity, Altered; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014732:Vibration
chemical_list: C107440:ABLIM1 protein, human; C478159:COL4A5 protein, human; D024141:Collagen Type IV; D005353:Fibronectins; D060588:LIM Domain Proteins; C486778:MTSS1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D053495:Osteopontin; D007633:Keratins