Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage

被引:12
作者
Muller, Petr [1 ]
Coates, Philip J. [1 ]
Nenutil, Rudolf [1 ]
Trcka, Filip [1 ]
Hrstka, Roman [1 ]
Chovanec, Josef [1 ]
Brychtova, Veronika [1 ]
Vojtesek, Borivoj [1 ]
机构
[1] Masaryk Mem Canc Inst, Zluty Kopec 7, Brno 65653, Czech Republic
基金
欧盟地平线“2020”;
关键词
Tomm34; Chaperone; Epithelial ovarian cancer; Tumour; Immunohistochemistry; Ovary; Heat shock protein; INVASIVE BREAST-CANCER; THERAPEUTIC TARGET; PROTEIN IMPORT; HUMAN COLON; HSP90; HSP70; CARCINOMA; NETWORK; TOM34; PHOSPHORYLATION;
D O I
10.1186/s13048-019-0498-0
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
BackgroundIncreased activity of the chaperones Hsp70 and Hsp90 is a common feature of solid tumours. Translocase of the outer mitochondrial membrane 34 (Tomm34) is a cochaperone of both Hsp70 and Hsp90 that was found to be overexpressed in colorectal, hepatocellular, lung and breast carcinomas. The expression profile of Tomm34 in ovarian cancer has not been investigated. Therefore, the aim of the current study was to investigate the expression pattern of Tomm34 in ovarian carcinomas and analyse its correlation with clinico-pathological parameters.ResultsEpithelial ovarian cancers (140) were histologically classified based on their morphology and graded into two types comprising 5 histologic subgroups. Type I carcinomas comprise low grade serous (LGSC), clear cell (CCOC) and endometrioid (ENOC), type II comprises high grade serous carcinomas (HGSC) and solid, pseudoendometrioid, transitional carcinomas (SET). Tomm34 was more highly expressed in type II than type I carcinomas (p<0.0001). Comparing tumours based on the mutation in the TP53 gene revealed similar results, where mutant tumours exhibited significantly higher levels of Tomm34 (p<0.0001). The decreased levels of Tomm34 in type I carcinomas were particularly evident in clear cell and mucinous carcinomas. The expression of Tomm34 was also positively correlated with FIGO stage (r=0.23; p=0.007). Tomm34 levels also indicated poor prognosis for patients with mutant p53.ConclusionsOur data indicate that Tomm34 is commonly expressed at high levels in epithelial ovarian cancers, except for the clear cell and mucinous subtypes. The expression of Tomm34 corresponds with the dualistic model of ovarian cancer pathogenesis where high grade, type II tumours exhibit higher expression of Tomm34 in contrast to type I tumours. These data are also comparable to the previous findings that Tomm34 is a marker of progression and poor prognosis in human cancer.
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页数:7
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共 48 条
  • [1] Ahmed MAH, 2018, PATHOL ONCOL RES
  • [2] Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification
    Aleskandarany, Mohammed A.
    Soria, D.
    Green, A. R.
    Nolan, C.
    Diez-Rodriguez, Maria
    Ellis, I. O.
    Rakha, E. A.
    [J]. BREAST CANCER RESEARCH AND TREATMENT, 2015, 151 (02) : 325 - 333
  • [3] TOMM34 expression in early invasive breast cancer: a biomarker associated with poor outcome
    Aleskandarany, Mohammed A.
    Negm, Ola H.
    Rakha, Emad A.
    Ahmed, Mohamed A. H.
    Nolan, Christopher C.
    Ball, Graham R.
    Caldas, Carlos
    Green, Andrew R.
    Tighe, Patrick J.
    Ellis, Ian O.
    [J]. BREAST CANCER RESEARCH AND TREATMENT, 2012, 136 (02) : 419 - 427
  • [4] Mitochondrial protein quality control in health and disease
    Baker, Michael J.
    Palmer, Catherine S.
    Stojanovski, Diana
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2014, 171 (08) : 1870 - 1889
  • [5] Integrated genomic analyses of ovarian carcinoma
    Bell, D.
    Berchuck, A.
    Birrer, M.
    Chien, J.
    Cramer, D. W.
    Dao, F.
    Dhir, R.
    DiSaia, P.
    Gabra, H.
    Glenn, P.
    Godwin, A. K.
    Gross, J.
    Hartmann, L.
    Huang, M.
    Huntsman, D. G.
    Iacocca, M.
    Imielinski, M.
    Kalloger, S.
    Karlan, B. Y.
    Levine, D. A.
    Mills, G. B.
    Morrison, C.
    Mutch, D.
    Olvera, N.
    Orsulic, S.
    Park, K.
    Petrelli, N.
    Rabeno, B.
    Rader, J. S.
    Sikic, B. I.
    Smith-McCune, K.
    Sood, A. K.
    Bowtell, D.
    Penny, R.
    Testa, J. R.
    Chang, K.
    Dinh, H. H.
    Drummond, J. A.
    Fowler, G.
    Gunaratne, P.
    Hawes, A. C.
    Kovar, C. L.
    Lewis, L. R.
    Morgan, M. B.
    Newsham, I. F.
    Santibanez, J.
    Reid, J. G.
    Trevino, L. R.
    Wu, Y. -Q.
    Wang, M.
    [J]. NATURE, 2011, 474 (7353) : 609 - 615
  • [6] Blesa JR, 2008, BIOCHEM CELL BIOL, V86, P46, DOI [10.1139/O07-151, 10.1139/o07-151]
  • [7] Heat Shock Proteins Promote Cancer: It's a Protection Racket
    Calderwood, Stuart K.
    Gong, Jianlin
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 2016, 41 (04) : 311 - 323
  • [8] Cancer of the ovary
    Cannistra, SA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (24) : 2519 - 2529
  • [9] Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing
    Chandel, Navdeep S.
    Jasper, Heinrich
    Ho, Theodore T.
    Passegue, Emmanuelle
    [J]. NATURE CELL BIOLOGY, 2016, 18 (08) : 823 - 832
  • [10] Characterization of the novel mitochondrial protein import component, Tom34, in mammalian cells
    Chewawiwat, N
    Yano, M
    Terada, K
    Hoogenraad, NJ
    Mori, M
    [J]. JOURNAL OF BIOCHEMISTRY, 1999, 125 (04) : 721 - 727