Noxa in colorectal cancer: a study on DNA, mRNA and protein expression.
Noxa is a BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Among them, Noxa protein expression was investigated with immunohistochemistry in 16 tumors and six corresponding normal mucosa samples. Further, we searched for Noxa mutations in all the cases using single-stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumors, and decreased in 9% and increased in 16% of the tumors compared with the normal mucosa; however, these changes did not have any clinical or pathological significance. The protein level in most of the cases investigated was correlated with the mRNA level. We did not find any mutations in the Noxa gene. Thus, we suggest that Noxa may not be of importance in the development of colorectal cancer.
Jansson
Agneta K
AK
Division of Oncology, Department of Biomedicine and Surgery, Linköping University, S-581 85 Linköping, Sweden. agnja@ibk.liu.se
Emterling
Anna M
AM
Arbman
Gunnar
G
Sun
Xiao-Feng
XF
D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D006801:Humans; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D004247:DNA