Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition

Tong, Yunguang; Tan, Yan‐Xi; Zhou, Cuiqi; Melmed, Shlomo

doi:10.1038/sj.onc.1210339

Cited by 78 publications

(72 citation statements)

References 30 publications

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“…Specifically in prostate cancer, it has been observed that LNCaP cells stably transfected with a PTTG1 construct showed higher S and G 2 -M percentages than vector-only transfectants. Reciprocally, LNCaP cells stably transfected with an antisense PTTG1 construct showed increased G 1 phase cells, as compared with control cells (33), a finding that was in accordance with siRNA PTTG1 effects reported in JEG-3 cells (34).…”

Section: Discussionsupporting

confidence: 74%

Prostate Cancer Cell Response to Paclitaxel Is Affected by Abnormally Expressed Securin PTTG1

Castilla

Medina

et al. 2014

Molecular Cancer Therapeutics

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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 slippageprone 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. Mol Cancer Ther; 13(10); 2372-83. Ó2014 AACR.

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Section: Discussionsupporting

confidence: 74%

Prostate Cancer Cell Response to Paclitaxel Is Affected by Abnormally Expressed Securin PTTG1

Castilla

Medina

et al. 2014

Molecular Cancer Therapeutics

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“…We did not observe any changes in the mutant mammary glands in the expression of c-Myc, Fgf2, or cyclin D3 as previously reported (21,22). Cyclin D1 (Ccnd1) is essential for the proliferation of mammary gland epithelial cells (23,24).…”

Section: Significancesupporting

confidence: 59%

“…In vitro chromatin immunoprecipitation experiments suggested the involvement of PTTG1 in global transcription regulation, probably through interaction with SP1 (10,22). Our analyses indicate that the transcription-regulating function of PTTG1 is important for mammary gland development in mice, although the exact mechanism remains to be determined.…”

Section: Discussionmentioning

confidence: 76%

Pttg1/securin is required for the branching morphogenesis of the mammary gland and suppresses mammary tumorigenesis

Hatcher

Dong

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Pituitary tumor transforming gene 1 (Pttg1) encodes the mammalian securin, which is an inhibitor of separase (a protease required for the separation of sister chromatids in mitosis and meiosis). PTTG1 is overexpressed in a number of human cancers and has been suggested to be an oncogene. However, we found that, in Pttg1-mutant females, the mammary epithelial cells showed increased proliferation and precocious branching morphogenesis. In accord with these phenotypic changes, progesterone receptor, cyclin D1, and Mmp2 were up-regulated whereas p21 (Cdkn1a) was down-regulated. These molecular changes provide explanation for the observed developmental defects, and suggest that Pttg1 is a tumor suppressor. Indeed, mice lacking Pttg1 developed spontaneous mammary tumors. Furthermore, in human breast tumors, PTTG1 protein levels were down-regulated and the reduction was significantly correlated with the tumor grade.

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“…About 400 targets were identified and categorized into three major functional groups involved in cell cycle, metabolic control or signal transduction pathways. 5 Meanwhile, p53, E2F1, Sp1 and some other transcriptional factors bind to the PTTG1 promoter, 21 indicating that PTTG1 accepts regulation from different pathways as well. These findings help us to understand the multifunctional character of PTTG1.…”

confidence: 99%

“…PTTG1 small interfering RNA (siRNA) treatment decreases the level of cyclin D3, increases the number of cells in G 1 phase and decreases cells in S phase. 5 In human cells, hPTTG1 binds to Ku-70, the regulatory subunit of the DNA-PK, an enzyme involved in repairing DNA double-strand breaks.…”

mentioning

confidence: 99%

Pituitary tumor-transforming gene 1: Perspective on an apoptosis pathway

Zhao¹,

Zhang²

2011

Cancer Biology & Therapy

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Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition

Cited by 78 publications

References 30 publications

Prostate Cancer Cell Response to Paclitaxel Is Affected by Abnormally Expressed Securin PTTG1

Prostate Cancer Cell Response to Paclitaxel Is Affected by Abnormally Expressed Securin PTTG1

Pttg1/securin is required for the branching morphogenesis of the mammary gland and suppresses mammary tumorigenesis

Pituitary tumor-transforming gene 1: Perspective on an apoptosis pathway

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