TRAP1 is Involved in Cell Cycle Regulated by Retinoblastoma Susceptibility Gene (RB1) in Early Hypoxia and has Variable Expression Patterns in Human Tumors

Authors

  • Jiangting Hu Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
  • Ern Yu Tan Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
  • Leticia Campo Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
  • Russell Leek Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
  • Zainina Seman Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
  • Helen Turley Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
  • Domenico Delia Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano, Italy
  • Alfredo Cesario Rehabilitative Pneumology, IRCCS, San Raffaele Pisana, Rome, Italy
  • Kevin Gatter Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
  • Francesco Pezzella Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK

DOI:

https://doi.org/10.6000/1929-2279.2013.02.03.5

Keywords:

TRAP1, RB1, cell cycle, chaperon, hypoxia.

Abstract

 Tumor necrosis factor receptor associated protein 1(TRAP1) is a member of the Hsp90 family that acts as a molecular chaperon to the tumor suppressor retinoblastoma susceptibility gene (RB1). We have previously demonstrated that TRAP1-positive cells contain a high level of cell proliferating genes, whilst TRAP1-negative cells contain a high level of genes involved in cell cycles and metastases. In this study, we performed a functional analysis of TRAP1 which focused on its regulation within a cell cycle in relation to RB1. Following a heat shock, TRAP1 translocates to the nucleus and chaperonsRB1. When TRAP1 is silenced by siRNA, or prevented from entering the nucleus in hypoxic cells, formation of RB1/E2F1 complexes is impaired and cell cycle activity is promoted by deregulating the G1/S transition. Inhibition of the nuclear translocation of TRAP1 with geldanamycin abrogates its ability to maintain RB1 in a form that associates with E2F1. Restoration of TRAP1 expression reverses these effects. We analysed TRAP1/RB1 expression on 630 tumors by immunohistochemical staining and found TRAP1 lost in some types of cancer, such as non-small cell lung cancer and breast cancer, and the positive correlation of TRAP1 expression in nuclear and cytoplasm with RB1 was observed. Clinico-pathological data showed that breast carcinoma patients lacking nuclear TRAP1 have a shorter disease free survival. Our data suggests that nuclear translocation of TRAP1 is crucial for its function as a chaperon. The loss of TRAP1 expression in certain types of cancer may provide the growth advantage due to the lost control at cell cycle check point.

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Published

2013-09-28

How to Cite

Jiangting Hu, Ern Yu Tan, Leticia Campo, Russell Leek, Zainina Seman, Helen Turley, Domenico Delia, Alfredo Cesario, Kevin Gatter, & Francesco Pezzella. (2013). TRAP1 is Involved in Cell Cycle Regulated by Retinoblastoma Susceptibility Gene (RB1) in Early Hypoxia and has Variable Expression Patterns in Human Tumors . Journal of Cancer Research Updates, 2(3), 194–210. https://doi.org/10.6000/1929-2279.2013.02.03.5

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Vol. 2 No. 3 (2013)

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