p27kip1: a target for tumor therapies?

Institute for Molecular Biology, Hannover Medical School, Hannover, Germany.
Cell Division (Impact Factor: 3.47). 02/2007; 2:13. DOI: 10.1186/1747-1028-2-13
Source: PubMed

ABSTRACT The cyclin kinase inhibitor p27kip1 acts as a potent tumor supressor protein in a variety of human cancers. Its expression levels correlate closely with the overall prognosis of the affected patient and often predict the outcome to different treatment modalities. In contrast to other tumor suppressor proteins p27 expression levels in tumor cells are frequently regulated by ubiquitin dependent proteolysis. Re-expression of p27 in cancer cells therefore does not require gene therapy but can be achieved by interfering with the protein turnover machinery. In this review we will summarize experimental results which highlight the potential use of p27 as a target for oncological therapies.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Molecular Aspects of Pituitary Tumorigenesis. Pituitary tumors, almost invariably adenomas, are of frequent occurrence, accounting for 10% to 15% of all the intracranial neoplasm. They are classi- fied as microadenomas (� 10 mm) or macroadenomas (! 10 mm) and as secreting or clinically non-secreting (or not functioning) adenomas. These tumors are autonomously capable to release pituitary hormones such as the growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The occurrence of metastases, charac- terizing a pituitary carcinoma, is exceedingly rare. However tumors with ag- gressive behavior, leading to local invasion, are relatively common. Although the pathogenesis of pituitary tumors is fully characterized, many molecular mechanisms of pituitary tumorigenesis had already been revealed. This re- view intents to describe advances in the understanding of the involved ad- vances that have been made in the last decade concerning pituitary tumors progression, including the participation of oncogenes, tumor suppressor genes and growth factors. (Arq Bras Endocrinol Metab. 2008; 52/4:599-610)
    Arquivos Brasileiros De Endocrinologia E Metabologia - ARQ BRAS ENDOCRINOL METABOL. 01/2008; 52(4).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Soon after the discovery of the Myc gene (c-Myc), it became clear that Myc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression have been described in many models. Also, the downregulation or inactivation of Myc results in the impairment of cell cycle progression. Given the frequent deregulation of Myc oncogene in human cancer it is importat to dissect out the mechanisms underlying the role of Myc on cell cycle control. Several parallel mechanisms account for Myc-mediated stimulation of cell cycle. First, most of the critical positive cell cycle regulators are encoded by genes induced by Myc. These Myc target genes include Cdks, cyclins and E2F transcription factors. Apart from its direct effects on the transcription, Myc is able to hyperactivate cyclin/Cdk complexes through the induction of Cdk activating kinase (CAK) and Cdc25 phosphatases. Moreover, Myc antagonizes the activity of cell cycle inhibitors as p21 and p27 through different mechanisms. Thus, Myc is able to block p21 transcription or to induce Skp2, a protein involved in p27 degradation. Finally, Myc induces DNA replication by binding to replication origins and by upregulating genes encoding proteins required for replication initiation. Myc also regulates genes involved in the mitotic control. A promising approach to treat tumors with deregulated Myc is the synthetic lethality based on the inhibition of Cdks. Thus, the knowledge of the Myc-dependent cell cycle regulatory mechanisms will help to discover new therapeutic approaches directed against malignancies with deregulated Myc. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 01/2014; · 5.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Malignant adrenocortical tumors are rare and highly aggressive; conversely benign tumors are common and frequently found incidentally, (the so-called incidentalomas). Currently, the use of molecular markers in the diagnosis of adrenocortical tumors is still controversial. Our aim was to analyze the molecular profile of different adrenocortical tumors with the purpose of identifying markers useful for the differential diagnosis between these tumors. The adrenocortical tumors that were studied (n=31) included non-functioning adenomas/incidentalomas (n=13), functioning adenomas with Cushing syndrome (n=7), and carcinomas (n=11); normal adrenal glands (n=12) were used as controls. For each sample, the percentage of the stained area for the markers StAR, IGF2, IGF-1R, p53, Mdm2, p21, p27, cyclin D1, Ki-67, β-catenin and E-cadherin was quantified using a morphometric computerized tool. IGF2, p27, cyclin D1 and Ki-67 were the markers whose percentage of stained area was significantly higher in carcinomas compared to adenomas. Ki-67 and p27 were the markers that showed the highest discriminative power for the differential diagnosis between carcinomas and all type of adenomas, while IGF2 and StAR only demonstrated to be useful for the diagnosis between carcinomas vs non-functioning adenomas and carcinomas vs adenomas with Cushing syndrome, respectively. The usefulness of Ki-67 has been recognized before in the differential diagnosis of malignancy. The additional use of p27 as an elective marker to distinguish benign from malignant adrenocortical tumors should be considered.
    Endocrine connections. 08/2013;

Full-text (2 Sources)

Available from
Jun 4, 2014

Similar Publications