Involvement of the Ink4a gene (p16 and p19arf) in murine tumorigenesis.
The INK4A and INK4B genes map to 9p21, with the INK4A gene encoding two products, p16 and p19ARF. Many neoplasms in which INK4A and INK4B genes are altered show deletions involving both genes. Mice carrying a targeted Ink4a deletion develop tumors at an early age. In the present study we examined the genetic alterations affecting the remaining Ink4a allele and the Ink4b gene in tumors arising in heterozygous Ink4a mice. We identified deletion of the remaining Ink4a allele in 7 of 18 (39%) tumors. We also observed deletion of the exon 1beta in 3 cases, one of them presenting this deletion as a unique alteration. In conclusion, the deletion of the remaining Ink4a allele was the alteration most frequently observed, representing the inactivation of two proteins capable of arresting the cell cycle through different pathways that involve the tumor suppressors pRB and p53.
Orlow
I
I
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Rabbani
F
F
Chin
L
L
Pomerantz
J
J
Ligeois
N
N
Dudas
M
M
Depinho
R
R
Cordón-Cardó
C
C
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004273:DNA, Neoplasm / Q000235:genetics; D017353:Gene Deletion; D018390:Gene Targeting; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000502:physiology; D025803:Tumor Suppressor Protein p14ARF
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D011506:Proteins; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF