Myristylation of FBR v-fos Dictates the Differentiation Pathways in Malignant Osteosarcoma

Myristylation of FBR v-fos, a c-fos retroviral homologue that causes osteosarcomas in mice, determines many of its transcriptional properties in vitro. To determine whether myristylation of FBR v-fos contributes to in vivo tumorigenicity, we examined its transforming capability in comparison to a no...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology 1996-10, Vol.135 (2), p.457-467
Main Authors: Jotte, Robert M., Holt, Jeffrey T.
Format: Article
Language:English
Subjects:
3T3 Cells
Adipocytes
Animals
Base Sequence
Cancer
Cell Differentiation
Cell lines
Cell Transformation, Neoplastic
Cells
Cellular biology
Collagens
Liposarcoma
Mice
Mice, Inbred BALB C
Mice, Transgenic
Moloney murine leukemia virus - genetics
Myristic Acid
Myristic Acids - metabolism
Oncogene Proteins v-fos - metabolism
Osteosarcoma
Osteosarcoma - genetics
Osteosarcoma - pathology
Polymerase Chain Reaction
Protein Processing, Post-Translational
Repetitive Sequences, Nucleic Acid
RNA
Sarcoma Viruses, Murine - genetics
Transgenic animals
Tumors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Myristylation of FBR v-fos, a c-fos retroviral homologue that causes osteosarcomas in mice, determines many of its transcriptional properties in vitro. To determine whether myristylation of FBR v-fos contributes to in vivo tumorigenicity, we examined its transforming capability in comparison to a nonmyristylated FBR v-fos (G2A-R). Retroviral infections with FBR v-fos and G2A-R transform BALB/c-3T3 cells. The number, size, and cellular morphology of foci generated by both FBR and G2A-R are indistinguishable. However, marked biological differences were found in transgenic mice expressing either the myristylated FBR v-fos or the nonmyristylated G2A-R. 11 of 26 FBR v-fos transgenic mice died as a result of gross tumor burden. None of the 28 G2A-R transgenic mice died from tumor burden, and only two of the G2A-R mice developed bone tumors. Histologic examination of the tumors reveals that the FBR v-fos bone tumors contain malignant cells with features of four cell lineages (osteocytes, chondrocytes, myocytes, and adipocytes) in an environment rich in extracellular matrix (ECM). However, the G2A-R tumors exist in an environment devoid of ECM and display malignant cells with features of adipocytes. Masson staining reveals that the ECM of the FBR tumors stains strongly for collagen. Immunohistochemical staining with collagen III antibody demonstrates an abundance of collagen III expression in this ECM. While NH2-terminal myristylation is not required for FBR immortalization and transformation, it is essential in determining the degree of differentiation and tumorigenicity of malignant cells.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.135.2.457