title: Loss of the retinoblastoma tumor suppressor protein in murine calvaria facilitates immortalization of osteoblast-adipocyte bipotent progenitor cells characterized by low expression of N-cadherin.
abstract: The retinoblastoma gene, RB1, is frequently inactivated in a subset of tumors, including retinoblastoma and osteosarcoma (OS). One characteristic of OS, as well as other tumors in which RB1 is frequently inactivated, is the lack of N-cadherin-mediated cell-cell adhesions. The frequent inactivation of RB1 and parallel loss of N-cadherin expression in OS prompted us to ask whether these observations are directly related to each other. In this study, we observed reduced N-cadherin expression in RB1(-/-) calvarial osteoblasts. In addition, RB1(-/-) cell lines had increased migration potential compared to their RB1(+/+) counterparts. These properties of RB1(-/-) cell lines correlated with an adipogenic potential lacking in RB1(+/+) cell lines, suggesting that each property is present in an immature progenitor cell. The isolation of a cell population with low surface expression of N-cadherin and enhanced adipogenic ability supports this view. Interestingly, the acute loss of pRb does not affect N-cadherin expression or migration or confer adipogenic potential to immortalized RB1(+/+) calvarial cells, suggesting that these traits are not a direct consequence of pRb loss; rather, pRb loss leads to the expansion and immortalization of an immature progenitor pool characterized by these properties.
authors.affiliation: Molecular Oncology Research Institute, Tufts Medical Center, and Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Gündüz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kong
authors.forename: Crystal D
authors.initials: CD
authors.lastname: Bryan
authors.forename: Philip W
authors.initials: PW
authors.lastname: Hinds
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015820:Cadherins; C489083:Cdh2 protein, mouse; D017931:DNA Primers; D012333:RNA, Messenger; D016160:Retinoblastoma Protein