Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish.
We have characterized 28 zebrafish lines with heterozygous mutations in ribosomal protein (rp) genes, and found that 17 of these are prone to develop zebrafish malignant peripheral nerve sheath tumors (zMPNST). Heterozygotes from the vast majority of tumor-prone rp lines were found to be growth-impaired, though not all growth-impaired rp lines were tumor-prone. Significantly, however, the rp lines with the greatest incidence of zMPNSTs all displayed a growth impairment. Furthermore, heterozygous cells from one tumor-prone rp line were out-competed by wild-type cells in chimeric embryos. The growth impairment resulting from heterozygosity for many rp genes suggests that a global defect in protein translation exists in these lines, raising the possibility that a translation defect that precedes tumor development is predictive of tumorigenesis.
Lai
Kevin
K
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Amsterdam
Adam
A
Farrington
Sarah
S
Bronson
Roderick T
RT
Hopkins
Nancy
N
Lees
Jacqueline A
JA
D000818:Animals; D002678:Chimera / Q000033:anatomy & histology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004198:Disease Susceptibility; D055785:Gene Knockdown Techniques; D009154:Mutation; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D012269:Ribosomal Proteins; D029961:Zebrafish Proteins