The primary structure of the putative oncogene pim-1 shows extensive homology with protein kinases

ArticleinCell 46(4):603-11 · September 1986with6 Reads
DOI: 10.1016/0092-8674(86)90886-X · Source: PubMed
Abstract
We have shown previously that the putative oncogene pim-1 is frequently activated by provirus insertion in murine leukemia virus-induced T cell lymphomas. Here we describe the structure of the pim-1 gene as determined by sequencing genomic and cDNA clones. The gene has an open reading frame, encoding a protein of 313 amino acids, extending over six exons and preceded and followed by stop codons in all reading frames. Proviruses always integrate outside the protein-encoding domain, showing a high preference for a small region in the 3'-terminal exon; integration in the 3' exon results in relatively high levels of pim-1 mRNA. Computer search reveals homology between pim-1 and protein kinases: all the domains characteristic of protein kinases are conserved in the pim-1 amino acid sequence. The highest homologies were observed with the protein-serine kinases.
    • "More recently, Pim2 has been shown to phosphorylate the ribosomal protein 4E-BP1, affecting protein synthesis [34]. Elevated levels of Pim1 kinase were first reported in human leukemia and lymphomas [8,35,36]. Recently, Pim1 was found to be increased in solid tumors, including pancreatic, prostate and bladder cancers37383940, as well as squamous cell carcinoma, gastric, colorectal and liver carcinomas [41,42], and liposarcoma [43]. Increased levels of Pim2 kinase have been detected in various lymphomas as well as in prostate cancer [44]. "
    [Show abstract] [Hide abstract] ABSTRACT: Citation: Grassow MN, Aparicio CB, Cecilia Y, Perez M, Galvan SM, et al. (2014) Pim1 Kinase Cooperates with Hormone Treatment to Promote Bladder and Ureteral Urothelial Hyperplasia. J Carcinog Mutagen 5: 161. doi:10.4172/2157-2518.1000161 Copyright: © 2014 Grassow MN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract The Pim serine/threonine kinases have been shown to be overexpressed in cancer. Elevated levels of Pim1 kinase were demonstrated in human leukemia and lymphomas, as well as in solid tumors such as pancreatic, prostate and bladder cancers, and have been proposed as a prognostic marker. Although the Pim kinases have been identified as oncogenes in transgenic mouse models, they have only weak transforming abilities on their own. However, they have been shown to greatly enhance the ability of other genes or chemical carcinogens to induce tumors. To explore the role of Pim1 in bladder and ureteral urothelial cancer, we generated a conditional Pim1 transgenic mouse model and found that prostate specific antigen-(PSA)-driven Cre expression lead to transgene expression in the bladder upon (testosterone/estrogen) hormone treatment. We then explored the effect of Pim1 overexpression on hormone treatment, either alone or in combination with Pten haploinsufficiency. We found that Pim1 overexpression increased the severity of bladder and ureteral urothelial hyperplasias in both backgrounds, leading to pyelonephritis in transgenic animals. Our data suggest that Pim1 might contribute to progression, rather than initiation, and that the hyperplasias also contribute to the development of pyelonephritis.
    Full-text · Article · Feb 2014 · PLoS ONE
    • "More recently, Pim2 has been shown to phosphorylate the ribosomal protein 4E-BP1, affecting protein synthesis [34]. Elevated levels of Pim1 kinase were first reported in human leukemia and lymphomas [8,35,36]. Recently, Pim1 was found to be increased in solid tumors, including pancreatic, prostate and bladder cancers37383940, as well as squamous cell carcinoma, gastric, colorectal and liver carcinomas [41,42], and liposarcoma [43]. Increased levels of Pim2 kinase have been detected in various lymphomas as well as in prostate cancer [44]. "
    Article · Feb 2014
    • "Elevated levels of Pim1 kinase were first reported in human leukemia and lymphomas [8], [38], [39]. Recently, Pim1 was found to be increased in solid tumors, including pancreatic and prostate cancers, squamous cell carcinoma, gastric, colorectal and liver carcinomas [40], [41], and liposarcoma [42]. "
    [Show abstract] [Hide abstract] ABSTRACT: The Pim proteins are a family of highly homologous protein serine/threonine kinases that have been found to be overexpressed in cancer. Elevated levels of Pim1 kinase were first discovered in human leukemia and lymphomas. However, more recently Pim1 was found to be increased in solid tumors, including pancreatic and prostate cancers, and has been proposed as a prognostic marker. Although the Pim kinases have been identified as oncogenes in transgenic models, they have weak transforming abilities on their own. However, they have been shown to greatly enhance the ability of other genes or chemical carcinogens to induce tumors. To explore the role of Pim1 in prostate cancer, we generated conditional Pim1 transgenic mice, expressed Pim1 in prostate epithelium, and analyzed the contribution of PIM1 to neoplastic initiation and progression. Accordingly, we explored the effect of PIM1 overexpression in 3 different settings: upon hormone treatment, during aging, and in combination with the absence of one Pten allele. We have found that Pim1 overexpression increased the severity of mouse prostate intraepithelial neoplasias (mPIN) moderately in all three settings. Furthermore, Pim1 overexpression, in combination with the hormone treatment, increased inflammation surrounding target tissues leading to pyelonephritis in transgenic animals. Analysis of senescence induced in these prostatic lesions showed that the lesions induced in the presence of inflammation exhibited different behavior than those induced in the absence of inflammation. While high grade prostate preneoplastic lesions, mPIN grades III and IV, in the presence of inflammation did not show any senescence markers and demonstrated high levels of Ki67 staining, untreated animals without inflammation showed senescence markers and had low levels of Ki67 staining in similar high grade lesions. Our data suggest that Pim1 might contribute to progression rather than initiation in prostate neoplasia.
    Full-text · Article · May 2013
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