title: TCam-2 seminoma cell line exhibits characteristic foetal germ cell responses to TGF-beta ligands and retinoic acid.
abstract: Germ cell testicular cancer is understood to arise during embryogenesis, based on the persistence of embryonic germ cell markers in carcinoma in situ and seminoma. In this study, we examine the potential of the seminoma-derived TCam-2 cell line to be used as representative in functional analyses of seminoma. We demonstrate expression of several early germ cell markers, including BLIMP1, OCT3/4, AP2γ, NANOG and KIT. Many TGF-beta superfamily receptors and downstream transcription factors are also present in these cells including the normally foetal ACTRIIA receptor, indicating potential responsiveness to TGF-beta superfamily ligands. Treatment with BMP4 or RA induces a significant increase in ACTRIA, ACTRIIA and ACTRIIB transcripts, whereas activin A decreases ACTRIB. BMP4 and RA each support TCam-2 survival and/or proliferation. In addition, despite increased KIT mRNA levels induced by BMP4, RA and activin A, activin A does not improve survival or proliferation. The capacity for BMP4 and retinoic acid to enhance foetal germ cell survival and proliferation/self-renewal has been demonstrated in mice, but not previously tested in humans. This study is the first to demonstrate a functional response in seminoma cells, using a well-characterized cell line, consistent with their foetal germ cell-like identity.
authors.affiliation: ARC Centre of Excellence in Biotechnology and Development, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic., Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Young
authors.forename: A
authors.initials: A
authors.lastname: Jaiprakash
authors.forename: S
authors.initials: S
authors.lastname: Mithraprabhu
authors.forename: C
authors.initials: C
authors.lastname: Itman
authors.forename: R
authors.initials: R
authors.lastname: Kitazawa
authors.forename: L H J
authors.initials: LH
authors.lastname: Looijenga
authors.forename: K L
authors.initials: KL
authors.lastname: Loveland
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism; D028341:Activins / Q000494:pharmacology; D033962:Adaptor Protein Complex 2 / Q000096:biosynthesis; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005854:Germ Cells / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D008024:Ligands; D008297:Male; D000071317:Nanog Homeobox Protein; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis; D018239:Seminoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D033962:Adaptor Protein Complex 2; C525809:BMP4 protein, human; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D018398:Homeodomain Proteins; D008024:Ligands; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; C087042:PRDM1 protein, human; D014212:Tretinoin; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019009:Proto-Oncogene Proteins c-kit; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A