The PMAIP1 gene on chromosome 18 is a candidate tumor suppressor gene in human pancreatic cancer.
Frequent loss of heterozygosity on the long arm of chromosome 18 is observed in pancreatic cancer. Previous studies suggested the existence of one or more tumor-suppressor genes other than SMAD4 on chromosome 18. To identify the candidate tumor-suppressor gene(s), we compared gene expression by cDNA microarray analyses using a pancreatic cancer cell line Panc-1 and its hybrid cell lines showing suppressed cell growth after introduction of one normal copy of chromosome 18. The microarray analyses identified 38 genes on chromosome 18 that showed differential expressional levels. Among these genes, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1/APR/NOXA) was identified as one of the candidates for tumor suppressor. Expression vector-mediated introduction of PMAIP1 suppressed cell proliferation, and RNAi-mediated knockdown of PMAIP1 induced recovery of cell growth. These results suggest that PMAIP1 may play an important role in the progression of pancreatic cancer.
Ishida
Masaharu
M
Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Sunamura
Makoto
M
Furukawa
Toru
T
Lefter
Liviu P
LP
Morita
Rina
R
Akada
Masanori
M
Egawa
Shinichi
S
Unno
Michiaki
M
Horii
Akira
A
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D046228:Microarray Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D034622:RNA Interference; D014183:Transplantation, Heterologous
C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2