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Gene Review

PTTG1  -  pituitary tumor-transforming 1

Homo sapiens

Synonyms: EAP1, Esp1-associated protein, HPTTG, PTTG, Pituitary tumor-transforming gene 1 protein, ...
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Disease relevance of PTTG1

  • INTERPRETATION: Increased tumour PTTG1 expression may be a marker of invasive colorectal carcinoma and could represent a new therapeutic target [1].
  • FINDINGS: PTTG1 was overexpressed in all of 48 colon carcinomas (median fold-increase 2.2 [IQR 1.8-3.3]) and in 19 of 20 colonic polyps (2.2 [1.6-3.1]) compared with normal colonic tissue [1].
  • METHODS: PTTG1 gene and protein expression were assessed in 68 colorectal tumours and compared with invasive characteristics, such as lymph-node invasion, evidence of metastases, tumour vessel density, and expression of basic fibroblast growth factor [1].
  • PTIG1 gene silencing using siRNA may be an effective modality to treat liver cancer, in which PTTG1 is abundantly expressed [2].
  • Ad.PTTG1-siRNA-mediated cytotoxic effect was dependent on expression levels of PTTG1 and p53 in hepatoma cell lines [2].
  • Taken together, our data suggest that the reported overexpression of PTTG and PBF in differentiated thyroid cancer has profound implications for activity of the NIS gene, and hence significantly impacts upon the efficacy of radioiodine treatment [3].
  • We also summarize the issue of PTTG expression and its correlation with clinicopathologic parameters in patients with neoplasms, particularly of endocrine organs [4].

High impact information on PTTG1

  • Differently regulated APCs (APC(Cdh1), APC(Ama1)) have not been implicated in securin degradation at meiosis I [5].
  • This is especially true of the anaphase promoting complex (APC), the machine that triggers chromosome segregation and the exit of mitosis by targeting securin and mitotic cyclins for destruction [6].
  • Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis [7].
  • The PTTG1 protein is cell-cycle regulated and was identified as the human securin (a category of proteins involved in the regulation of sister-chromatid separation) on the basis of biochemical similarities with the Pds1p protein of budding yeast and the Cut2p protein of fission yeast [7].
  • Moreover, we observed that transfection of H1299 cells with securin induced an accumulation of G2 cells that compensated for the loss of G2 cells caused by transfection with p53 [7].

Chemical compound and disease context of PTTG1


Biological context of PTTG1


Anatomical context of PTTG1

  • Invasion of surrounding lymph nodes was associated with higher PTTG1 expression than in carcinomas limited to the bowel wall (3.4 [2.1-5.9] vs 1.9 [1.7-2.4], p=0.007), and higher PTTG1 expression was seen in more vascular than in less vascular tumours (2.6 [1.9-5.1] vs 1.9 [1.8-2.5], p=0.04) [1].
  • Murine PTTG (mPTTG) is 66% homologous to human PTTG1 and PTTG-null (PTTG-/-) mice exhibit pancreatic beta-cell hypoplasia and abnormal nuclear morphology with resultant diabetes [15].
  • Pituitary tumor transforming gene 1 (PTTG1) recently cloned from human testis is a potent oncogene and is highly expressed in all the tumors analyzed to date [16].
  • In normal tissues, expression of PTTG1 mRNA was very low or undetectable except in testis, where PTTG1 mRNA was found to be localized to spermatocytes and spermatids [16].
  • Our studies revealed a high level of expression of PTTG1 mRNA in both seminomatous and non-seminomatous testicular tumors; epithelial, sex-cord and stromal cell, and germ cell tumors of the ovary; and invasive ductal, ductal in situ and infiltrating ductal carcinoma of the breast [16].

Associations of PTTG1 with chemical compounds


Physical interactions of PTTG1

  • Pull-down and co-immunoprecipitation assays demonstrated that p53 interacts specifically with securin both in vitro and in vivo [7].
  • The PTTG binding domain in PBF was located within the C-terminal 30-amino acid region that contain a nuclear localization signal [19].
  • Securin is an inhibitory protein that is bound to a protease called Separase to inhibit sister chromatid separation until the onset of anaphase [20].
  • Using biotin-streptavidin pull-down assays, we confirmed Oct-1 binding to the two octamer motifs in the hPTTG1 promoter (-1669/-1631 and -1401/-1361) [21].

Regulatory relationships of PTTG1

  • Securin also inhibits the ability of p53 to induce cell death [7].
  • Separase is activated by the degradation of its inhibitor securin and by the removal of inhibitory phosphates [22].
  • Human pituitary tumor-transforming gene (PTTG1) motif suppresses prolactin expression [13].
  • In NT-2 cells, securin stimulated FGF-2 expression, which could be abrogated by a carboxyl-terminal mutation [23].
  • Furthermore, in U87 cells PTTG expression was up-regulated by promalignant ligands epithelial growth factor (EGF) and TGFalpha, both at the protein and mRNA levels [24].

Other interactions of PTTG1


Analytical, diagnostic and therapeutic context of PTTG1


  1. Expression of pituitary-tumour transforming gene in colorectal tumours. Heaney, A.P., Singson, R., McCabe, C.J., Nelson, V., Nakashima, M., Melmed, S. Lancet (2000) [Pubmed]
  2. Adenovirus-mediated transfer of siRNA against PTTG1 inhibits liver cancer cell growth in vitro and in vivo. Cho-Rok, J., Yoo, J., Jang, Y.J., Kim, S., Chu, I.S., Yeom, Y.I., Choi, J.Y., Im, D.S. Hepatology (2006) [Pubmed]
  3. PTTG and PBF repress the human sodium iodide symporter. Boelaert, K., Smith, V.E., Stratford, A.L., Kogai, T., Tannahill, L.A., Watkinson, J.C., Eggo, M.C., Franklyn, J.A., McCabe, C.J. Oncogene (2007) [Pubmed]
  4. Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. Salehi, F., Kovacs, K., Scheithauer, B.W., Lloyd, R.V., Cusimano, M. Endocr. Relat. Cancer (2008) [Pubmed]
  5. Mnd2, an essential antagonist of the anaphase-promoting complex during meiotic prophase. Penkner, A.M., Prinz, S., Ferscha, S., Klein, F. Cell (2005) [Pubmed]
  6. Recycling the cell cycle: cyclins revisited. Murray, A.W. Cell (2004) [Pubmed]
  7. Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis. Bernal, J.A., Luna, R., Espina, A., Lázaro, I., Ramos-Morales, F., Romero, F., Arias, C., Silva, A., Tortolero, M., Pintor-Toro, J.A. Nat. Genet. (2002) [Pubmed]
  8. Pituitary Tumor Transforming Gene (PTTG) Stimulates Thyroid Cell Proliferation via a Vascular Endothelial Growth Factor/Kinase Insert Domain Receptor/Inhibitor of DNA Binding-3 Autocrine Pathway. Kim, D.S., Franklyn, J.A., Boelaert, K., Eggo, M.C., Watkinson, J.C., McCabe, C.J. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  9. Opposing securin and p53 protein expression in the oxaliplatin-induced cytotoxicity of human colorectal cancer cells. Chiu, S.J., Hsu, T.S., Chao, J.I. Toxicol. Lett. (2006) [Pubmed]
  10. PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Cristina, C., Díaz-Torga, G.S., Goya, R.G., Kakar, S.S., Perez-Millán, M.I., Passos, V.Q., Giannella-Neto, D., Bronstein, M.D., Becu-Villalobos, D. Mol. Cancer (2007) [Pubmed]
  11. Expression of hpttg proto-oncogene in lymphoid neoplasias. Sáez, C., Pereda, T., Borrero, J.J., Espina, A., Romero, F., Tortolero, M., Pintor-Toro, J.A., Segura, D.I., Japón, M.A. Oncogene (2002) [Pubmed]
  12. Pituitary tumor transforming gene overexpression facilitates pituitary tumor development. Donangelo, I., Gutman, S., Horvath, E., Kovacs, K., Wawrowsky, K., Mount, M., Melmed, S. Endocrinology (2006) [Pubmed]
  13. Human pituitary tumor-transforming gene (PTTG1) motif suppresses prolactin expression. Horwitz, G.A., Miklovsky, I., Heaney, A.P., Ren, S.G., Melmed, S. Mol. Endocrinol. (2003) [Pubmed]
  14. Ectopic expression of PTTG1/securin promotes tumorigenesis in human embryonic kidney cells. Hamid, T., Malik, M.T., Kakar, S.S. Mol. Cancer (2005) [Pubmed]
  15. Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells. Yu, R., Cruz-Soto, M., Calzi, S.L., Hui, H., Melmed, S. J. Endocrinol. (2006) [Pubmed]
  16. Molecular cloning of pituitary tumor transforming gene 1 from ovarian tumors and its expression in tumors. Puri, R., Tousson, A., Chen, L., Kakar, S.S. Cancer Lett. (2001) [Pubmed]
  17. Human pituitary tumor-transforming gene induces angiogenesis. Ishikawa, H., Heaney, A.P., Yu, R., Horwitz, G.A., Melmed, S. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  18. DNA damage-induced inhibition of securin expression is mediated by p53. Zhou, Y., Mehta, K.R., Choi, A.P., Scolavino, S., Zhang, X. J. Biol. Chem. (2003) [Pubmed]
  19. A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product. Chien, W., Pei, L. J. Biol. Chem. (2000) [Pubmed]
  20. Securin is a target of the UV response pathway in mammalian cells. Romero, F., Gil-Bernabé, A.M., Sáez, C., Japón, M.A., Pintor-Toro, J.A., Tortolero, M. Mol. Cell. Biol. (2004) [Pubmed]
  21. Oct-1 induces pituitary tumor transforming gene expression in endocrine tumors. Zhou, C., Tong, Y., Wawrowsky, K., Bannykh, S., Donangelo, I., Melmed, S. Endocr. Relat. Cancer (2008) [Pubmed]
  22. Regulation of human separase by securin binding and autocleavage. Waizenegger, I., Giménez-Abián, J.F., Wernic, D., Peters, J.M. Curr. Biol. (2002) [Pubmed]
  23. A potential role for PTTG/securin in the developing human fetal brain. Boelaert, K., Tannahill, L.A., Bulmer, J.N., Kachilele, S., Chan, S.Y., Kim, D., Gittoes, N.J., Franklyn, J.A., Kilby, M.D., McCabe, C.J. FASEB J. (2003) [Pubmed]
  24. Expression of pituitary tumor transforming gene (PTTG) and its binding protein in human astrocytes and astrocytoma cells: function and regulation of PTTG in U87 astrocytoma cells. Tfelt-Hansen, J., Yano, S., Bandyopadhyay, S., Carroll, R., Brown, E.M., Chattopadhyay, N. Endocrinology (2004) [Pubmed]
  25. Calcium-sensing receptor induces messenger ribonucleic acid of human securin, pituitary tumor transforming gene, in rat testicular cancer. Tfelt-Hansen, J., Schwarz, P., Terwilliger, E.F., Brown, E.M., Chattopadhyay, N. Endocrinology (2003) [Pubmed]
  26. Identification of over-expressed genes in human renal cell carcinoma by combining suppression subtractive hybridization and cDNA library array. Ai, J., Zhang, Z., Xin, D., Zhu, H., Yan, Q., Xin, Z., Na, Y., Guo, Y. Sci. China, C, Life Sci. (2004) [Pubmed]
  27. Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells. Pei, L. J. Biol. Chem. (1999) [Pubmed]
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