PTTG1 expression is associated with hyperproliferative disease and poor prognosis in multiple myeloma

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11 Citations (Scopus)

Abstract

Background: Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of malignant plasma cells within the bone marrow. We have previously identified pituitary tumour transforming gene 1 (Pttg1) as a gene that is significantly upregulated in the haematopoietic compartment of the myeloma-susceptible C57BL/KaLwRij mouse strain, when compared with the myeloma-resistant C57BL/6 mouse. Over-expression of PTTG1 has previously been associated with malignant progression and an enhanced proliferative capacity in solid tumours. Methods: In this study, we investigated PTTG1 gene and protein expression in MM plasma cells from newly diagnosed MM patients. Gene expression profiling was used to identify gene signatures associated with high PTTG1 expression in MM patients. Additionally, we investigated the effect of short hairpin ribonucleic acid (shRNA)-mediated PTTG1 knockdown on the proliferation of the murine myeloma plasma cell line 5TGM1 in vitro and in vivo. Results: PTTG1 was found to be over-expressed in 36-70 % of MM patients, relative to normal controls, with high PTTG1 expression being associated with poor patient outcomes (hazard ratio 2.49; 95 % CI 1.28 to 4.86; p = 0.0075; log-rank test). In addition, patients with high PTTG1 expression exhibited increased expression of cell proliferation-associated genes including CCNB1, CCNB2, CDK1, AURKA, BIRC5 and DEPDC1. Knockdown of Pttg1 in 5TGM1 cells decreased cellular proliferation, without affecting cell cycle distribution or viability, and decreased expression of Ccnb1, Birc5 and Depdc1 in vitro. Notably, Pttg1 knockdown significantly reduced MM tumour development in vivo, with an 83.2 % reduction in tumour burden at 4 weeks (p < 0.0001, two-way ANOVA). Conclusions: This study supports a role for increased PTTG1 expression in augmenting tumour development in a subset of MM patients.

LanguageEnglish
Article number106
JournalJournal of Hematology and Oncology
Volume8
Issue number1
DOIs
Publication statusPublished - 6 Oct 2015

Keywords

  • Multiple myeloma
  • PTTG1
  • Proliferation/C57BL/KaLwRij

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

@article{a632fead88594b3e848a822bc99a199c,
title = "PTTG1 expression is associated with hyperproliferative disease and poor prognosis in multiple myeloma",
abstract = "Background: Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of malignant plasma cells within the bone marrow. We have previously identified pituitary tumour transforming gene 1 (Pttg1) as a gene that is significantly upregulated in the haematopoietic compartment of the myeloma-susceptible C57BL/KaLwRij mouse strain, when compared with the myeloma-resistant C57BL/6 mouse. Over-expression of PTTG1 has previously been associated with malignant progression and an enhanced proliferative capacity in solid tumours. Methods: In this study, we investigated PTTG1 gene and protein expression in MM plasma cells from newly diagnosed MM patients. Gene expression profiling was used to identify gene signatures associated with high PTTG1 expression in MM patients. Additionally, we investigated the effect of short hairpin ribonucleic acid (shRNA)-mediated PTTG1 knockdown on the proliferation of the murine myeloma plasma cell line 5TGM1 in vitro and in vivo. Results: PTTG1 was found to be over-expressed in 36-70 {\%} of MM patients, relative to normal controls, with high PTTG1 expression being associated with poor patient outcomes (hazard ratio 2.49; 95 {\%} CI 1.28 to 4.86; p = 0.0075; log-rank test). In addition, patients with high PTTG1 expression exhibited increased expression of cell proliferation-associated genes including CCNB1, CCNB2, CDK1, AURKA, BIRC5 and DEPDC1. Knockdown of Pttg1 in 5TGM1 cells decreased cellular proliferation, without affecting cell cycle distribution or viability, and decreased expression of Ccnb1, Birc5 and Depdc1 in vitro. Notably, Pttg1 knockdown significantly reduced MM tumour development in vivo, with an 83.2 {\%} reduction in tumour burden at 4 weeks (p < 0.0001, two-way ANOVA). Conclusions: This study supports a role for increased PTTG1 expression in augmenting tumour development in a subset of MM patients.",
keywords = "Multiple myeloma, PTTG1, Proliferation/C57BL/KaLwRij",
author = "Noll, {Jacqueline E.} and Kate Vandyke and Hewett, {Duncan R.} and Mrozik, {Krzysztof M.} and Bala, {Rachel J.} and Williams, {Sharon A.} and Kok, {Chung H.} and Zannettino, {Andrew C W}",
year = "2015",
month = "10",
day = "6",
doi = "10.1186/s13045-015-0209-2",
language = "English",
volume = "8",
journal = "Journal of Hematology and Oncology",
issn = "1756-8722",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - PTTG1 expression is associated with hyperproliferative disease and poor prognosis in multiple myeloma

AU - Noll, Jacqueline E.

AU - Vandyke, Kate

AU - Hewett, Duncan R.

AU - Mrozik, Krzysztof M.

AU - Bala, Rachel J.

AU - Williams, Sharon A.

AU - Kok, Chung H.

AU - Zannettino, Andrew C W

PY - 2015/10/6

Y1 - 2015/10/6

N2 - Background: Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of malignant plasma cells within the bone marrow. We have previously identified pituitary tumour transforming gene 1 (Pttg1) as a gene that is significantly upregulated in the haematopoietic compartment of the myeloma-susceptible C57BL/KaLwRij mouse strain, when compared with the myeloma-resistant C57BL/6 mouse. Over-expression of PTTG1 has previously been associated with malignant progression and an enhanced proliferative capacity in solid tumours. Methods: In this study, we investigated PTTG1 gene and protein expression in MM plasma cells from newly diagnosed MM patients. Gene expression profiling was used to identify gene signatures associated with high PTTG1 expression in MM patients. Additionally, we investigated the effect of short hairpin ribonucleic acid (shRNA)-mediated PTTG1 knockdown on the proliferation of the murine myeloma plasma cell line 5TGM1 in vitro and in vivo. Results: PTTG1 was found to be over-expressed in 36-70 % of MM patients, relative to normal controls, with high PTTG1 expression being associated with poor patient outcomes (hazard ratio 2.49; 95 % CI 1.28 to 4.86; p = 0.0075; log-rank test). In addition, patients with high PTTG1 expression exhibited increased expression of cell proliferation-associated genes including CCNB1, CCNB2, CDK1, AURKA, BIRC5 and DEPDC1. Knockdown of Pttg1 in 5TGM1 cells decreased cellular proliferation, without affecting cell cycle distribution or viability, and decreased expression of Ccnb1, Birc5 and Depdc1 in vitro. Notably, Pttg1 knockdown significantly reduced MM tumour development in vivo, with an 83.2 % reduction in tumour burden at 4 weeks (p < 0.0001, two-way ANOVA). Conclusions: This study supports a role for increased PTTG1 expression in augmenting tumour development in a subset of MM patients.

AB - Background: Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of malignant plasma cells within the bone marrow. We have previously identified pituitary tumour transforming gene 1 (Pttg1) as a gene that is significantly upregulated in the haematopoietic compartment of the myeloma-susceptible C57BL/KaLwRij mouse strain, when compared with the myeloma-resistant C57BL/6 mouse. Over-expression of PTTG1 has previously been associated with malignant progression and an enhanced proliferative capacity in solid tumours. Methods: In this study, we investigated PTTG1 gene and protein expression in MM plasma cells from newly diagnosed MM patients. Gene expression profiling was used to identify gene signatures associated with high PTTG1 expression in MM patients. Additionally, we investigated the effect of short hairpin ribonucleic acid (shRNA)-mediated PTTG1 knockdown on the proliferation of the murine myeloma plasma cell line 5TGM1 in vitro and in vivo. Results: PTTG1 was found to be over-expressed in 36-70 % of MM patients, relative to normal controls, with high PTTG1 expression being associated with poor patient outcomes (hazard ratio 2.49; 95 % CI 1.28 to 4.86; p = 0.0075; log-rank test). In addition, patients with high PTTG1 expression exhibited increased expression of cell proliferation-associated genes including CCNB1, CCNB2, CDK1, AURKA, BIRC5 and DEPDC1. Knockdown of Pttg1 in 5TGM1 cells decreased cellular proliferation, without affecting cell cycle distribution or viability, and decreased expression of Ccnb1, Birc5 and Depdc1 in vitro. Notably, Pttg1 knockdown significantly reduced MM tumour development in vivo, with an 83.2 % reduction in tumour burden at 4 weeks (p < 0.0001, two-way ANOVA). Conclusions: This study supports a role for increased PTTG1 expression in augmenting tumour development in a subset of MM patients.

KW - Multiple myeloma

KW - PTTG1

KW - Proliferation/C57BL/KaLwRij

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U2 - 10.1186/s13045-015-0209-2

DO - 10.1186/s13045-015-0209-2

M3 - Article

VL - 8

JO - Journal of Hematology and Oncology

T2 - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

SN - 1756-8722

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