The tumor suppressor rpl36 restrains KRAS(G12V)-induced pancreatic cancer.
Ribosomal proteins are known to be required for proper assembly of mature ribosomes. Recent studies indicate an additional role for ribosomal proteins as candidate tumor suppressor genes. Pancreatic acinar cells, recently identified as effective cells of origin for pancreatic adenocarcinoma, display especially high-level expression of multiple ribosomal proteins. We, therefore, functionally interrogated the ability of two ribosomal proteins, rpl36 and rpl23a, to alter the response to oncogenic Kras in pancreatic acinar cells using a newly established model of zebrafish pancreatic cancer. These studies reveal that rpl36, but not rpl23a, acts as a haploinsufficient tumor suppressor, as manifested by more rapid tumor progression and decreased survival in rpl36(hi1807/+);ptf1a:gal4VP16(Tg);UAS:GFP-KRAS(G12V) fish compared with their rpl36(+/+);ptf1a:gal4VP16;UAS:GFP-KRAS(G12V) siblings. These results suggest that rpl36 may function as an effective tumor suppressor during pancreatic tumorigenesis.
1 Department of Surgery, Johns Hopkins University , Baltimore, Maryland.
Elayne
E
Provost
Jennifer M
JM
Bailey
Sumar
S
Aldrugh
Shu
S
Liu
Christine
C
Iacobuzio-Donahue
Steven D
SD
Leach
D061354:Acinar Cells / Q000378:metabolism; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D016147:Genes, Tumor Suppressor; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008856:Microscopy, Fluorescence; D020125:Mutation, Missense / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
D017931:DNA Primers; D012269:Ribosomal Proteins; D029961:Zebrafish Proteins; C000599558:ribosomal protein L36, zebrafish; C000589775:Kras protein, zebrafish; D016283:Proto-Oncogene Proteins p21(ras)