Allison Simone Landman

Massachusetts Institute of Technology, Cambridge, MA, United States

Are you Allison Simone Landman?

Claim your profile

Publications (3)17.09 Total impact

  • A S Landman, P S Danielian, J A Lees
    [Show abstract] [Hide abstract]
    ABSTRACT: The pocket proteins pRB, p107 and p130 have established roles in regulating the cell cycle through the control of E2F activity. The pocket proteins regulate differentiation of a number of tissues in both cell cycle-dependent and -independent manners. Prior studies showed that mutation of p107 and p130 in the mouse leads to defects in cartilage development during endochondral ossification, the process by which long bones form. Despite evidence of a role for pRB in osteoblast differentiation, it is unknown whether it functions during cartilage development. Here, we show that mutation of Rb in the early mesenchyme of p107-mutant mice results in severe cartilage defects in the growth plates of long bones. This is attributable to inappropriate chondrocyte proliferation that persists after birth and leads to the formation of enchondromas in the growth plates as early as 8 weeks of age. Genetic crosses show that development of these tumorigenic lesions is E2f3 dependent. These results reveal an overlapping role for pRB and p107 in cartilage development, endochondral ossification and enchondroma formation that reflects their coordination of cell-cycle exit at appropriate developmental stages.Oncogene advance online publication, 12 November 2012; doi:10.1038/onc.2012.496.
    Oncogene 11/2012; · 7.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutation of the RB-1 and p53 tumor suppressors is associated with the development of human osteosarcoma. With the goal of generating a mouse model of this disease, we used conditional and transgenic mouse strains to inactivate Rb and/or p53 specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas with complete penetrance. These tumors display many of the characteristics of human osteosarcomas, including being highly metastatic. We established cell lines from the DKO osteosarcomas to further investigate their properties. These immortalized cell lines are highly proliferative and they retain their tumorigenic potential, as judged by their ability to form metastatic tumors in immunocompromised mice. Moreover, they can be induced to differentiate and, depending on the inductive signal, will adopt either the osteogenic or adipogenic fate. Consistent with this multipotency, a significant portion of these tumor cells express Sca-1, a marker that is typically associated with stem cells/uncommitted progenitors. By assaying sorted cells in transplant assays, we demonstrate that the tumorigenicity of the osteosarcoma cell lines correlates with the presence of the Sca-1 marker. Finally, we show that loss of Rb and p53 in Sca-1-positive mesenchymal stem/progenitor cells is sufficient to yield transformed cells that can initiate osteosarcoma formation in vivo.
    Proceedings of the National Academy of Sciences 09/2008; 105(33):11851-6. · 9.74 Impact Factor
  • Source
    Allison Simone Landman
    [Show abstract] [Hide abstract]
    ABSTRACT: Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2009. Vita. Cataloged from PDF version of thesis. Includes bibliographical references. pRB is a member of the pocket protein family, which includes the closely related proteins p107 and p130. The pocket proteins are critical regulators of the cell cycle and function to restrain proliferation by controlling the activity of the E2F family of transcription factors. The pocket proteins also play an important role in the development of many tissues. Due to the frequency of mutation of pRB in Osteosarcoma, and its role in the development of tissues of mesenchymal origin, we sought to understand the consequence of the loss of pRb, and its family member p107, in murine mesenchymal cells. The early lethality of Rb-/- mice hampers the study of many mesenchymal tissues, thus we conditionally deleted Rb in the mesenchymal progenitors of p107 mice. These mice develop embryonic skeletal abnormalities characterized by wider and shorter long bones and malformed sternums. Analysis of the defects revealed that inappropriate proliferation of chondrocytes in the growth plate contributed to the phenotype. Mutant adult mice displayed an exacerbated cartilage and growth plate phenotypes, which corresponded to ectopically proliferating growth plate chondrocytes and altered chondrocyte differentiation. Notably, these cartilage defects were consistently associated with the development of enchondromas, a cartilage neoplasm. We also examined the role of pRb, and its cooperation with the tumor suppressor p53, in the development of murine osteosarcoma. We examined the effect of mutation of Rb and p53 in bone marrow-derived mesenchymal cells, which contains the putative cell of origin of osteosarcoma. (cont.) We show that Rb and p53 are required for the proper differentiation of mesenchymal cells and mesenchymal cells deficient in these proteins are tumorigenic. These studies demonstrate that loss of pocket protein function in the mesenchymal lineages can be disastrous for an organism, resulting in tissue deformities and a predisposition to cancer. Thus, pocket proteins play a critical role in regulating skeletogenesis as well as in adult mesenchymal tissue homeostasis and tumor suppression. by Allison Simone Landman. Ph.D.