Cancer

Prostate cancer; Marginal zone B-cell lymphomas; Nodal marginal zone B-Cell lymphomas; Lung cancer; Diffuse large B-cell lymphomas (DLBCL)

PIM1 is a known oncoprotein (OP). The Pim1 protein is undergoes relatively little mutation in human tumours, about the same as typical proteins. The active form of the protein kinase normally acts to promote tumour cell proliferation. The oncogenic activity of the Pim-1 protein is mediated through the positive regulation of MYC transcription (another oncogene), the regulation of cell cycle progression, and by the inhibition of the pro-apoptotic proteins BAD, MAP3K5, and FOXO3. In addition, Pim-1 has been shown to promote genomic instability. Gain-of-function mutations in the Pim-1 gene resulting in the up-regulation of Pim-1 activity have been observed in several human cancer types, indicating a role in tumorigenesis. For example, significantly elevated Pim-1 expression was observed in several hematopoietic malignancies and in several solid tumours. In animal studies, over-expression of the Pim-1 protein in mice leads to an increased occurence of tumours, while the knockout of Pim-1 expression has no observable phenotypic consequence.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= -61, p<0.008); Cervical epithelial cancer (%CFC= +98, p<0.006); Classical Hodgkin lymphomas (%CFC= +49, p<0.002); Colorectal adenocarcinomas (early onset) (%CFC= +65, p<0.004); Large B-cell lymphomas (%CFC= +101, p<0.007); Oral squamous cell carcinomas (OSCC) (%CFC= -64, p<0.05); Skin fibrosarcomas (%CFC= -61); Skin melanomas - malignant (%CFC= -63, p<0.006); Skin squamous cell carcinomas (%CFC= +168, p<0.093); Vulvar intraepithelial neoplasia (%CFC= +58, p<0.035). The COSMIC website notes an up-regulated expression score for PIM1 in diverse human cancers of 418, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 2 for this protein kinase in human cancers was 97% lower than the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.09 % in 26039 diverse cancer specimens. This rate is only 20 % higher than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.55 % in 2221 haematopoietic and lymphoid cancers tested.

Most frequent mutations with the number of reports indicated in brackets: K24N (6); S97N (6).

Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.