Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, the pituitary tumor transforming gene 1 (PTTG1) has been suggested to be an oncogene. To investigate whether PTTG1 plays a positive role in the pathogenesis of prostate cancer, PTTG1 protein expression was examined in prostate tissue samples by immunohistochemistry. PTTG1 expression was detected in a high percentage of prostate cancer tissues (34/41, 82.9%), but to a much lesser extent in non-malignant tissues (5/14, 35.7%). To further confirm these results, the expression vectors containing either the PTTG1 or antisense-PTTG1 gene were transfected into a prostate cancer cell line, LNCaP, and the cell proliferation rate was studied, as well as tumorigenicity in the LNCaP cells expressing different levels of the PTTG1 protein. Ectopic PTTG1 gene expression promoted prostate cancer cell proliferation and tumorigenesis both in vitro and in nude mice. In contrast, down-regulation of PTTG1 led to suppression of tumor cell growth. These results suggest that PTTG1 may be a potential prognostic marker for prostate cancer and that the down-regulation of PTTG1 may be a therapeutic target in the suppression of prostate cancer growth.
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PMID:Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer. 1661 32

PTTG1 protein, the human securin, has a central role in sister chromatid separation during mitosis, and its altered expression has been reported in many tumor types. Paclitaxel is a widely used chemotherapeutic drug, whose mechanism of action is related to its ability to arrest cells in mitosis and the subsequent induction of the intrinsic apoptotic pathway. By using two prostate cancer cell lines with different responses to paclitaxel treatment, we have identified two situations in which PTTG1 influences cell fate differentially. In slippage-prone PC3 cells, both PTTG1 downregulation and overexpression induce an increase in mitotic cells that is associated with diminished apoptosis after paclitaxel treatment. In LNCaP cells, however, PTTG1 downregulation prevents mitotic entry and, subsequently, inhibits mitosis-associated, paclitaxel-induced apoptosis. In contrast, PTTG1 overexpression induces an increase in mitotic cells and apoptosis after paclitaxel treatment. We have also identified a role for Mcl-1 protein in preventing apoptosis during mitosis in PC3 cells, as simultaneous PTTG1 and Mcl-1 silencing enhances mitosis-associated apoptosis after paclitaxel treatment. The finding that a more efficient mitotic arrest alone in PC3 cells is not enough to increase apoptosis was also confirmed with the observation that a selected paclitaxel-resistant PC3 cell line showed an apoptosis-resistant phenotype associated with increased mitosis upon paclitaxel treatment. These findings could contribute to identify putative responsive and nonresponsive cells and help us to approach incomplete responses to paclitaxel in the clinical setting.
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PMID:Prostate cancer cell response to paclitaxel is affected by abnormally expressed securin PTTG1. 2512 70