HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth

Saija Haapa-Paananen, Santeri Kiviluoto, Marika Waltari, Marjut Puputti, John Mpindi, Pekka Kohonen, Olli Tynninen, Hannu Haapasalo, Heikki Joensuu, Merja Perälä, Olli Kallioniemi

Research output: Contribution to journalOther journal contributionScientificpeer-review

Abstract

Malignant glioma is the most common brain tumor with 16,000 individuals diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9,783 Affymetrix samples from the GeneSapiens database (www.genesapiens.org) to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared to 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (Hairy and Enhancer of Split 6) emerged as one of the most glioma-specific genes. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was also expressed in endothelial cells in normal and glioma tissues. Recurrent grade 2 astrocytomas and grade 2-3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. Functional studies implied a critical role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and induction of Caspase 3/7 activity after HES6 silencing in A172 and LN405 cells. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc, and NF-?B transcriptional networks. We conclude that HES6 has a critical role in sustaining glioma cell growth, survival, migration and possibly angiogenesis. HES6 is a potential therapeutic target and biomarker for glioma. This work was supported by funding under the 6th FP of the European Union, Project RIGHT (LSHB-CT-2004-005276), and the Academy of Finland.
Original languageEnglish
Article numberAbstract nr 3800
JournalCancer Research
Volume71
Issue number8 Suppl
DOIs
Publication statusPublished - 2011
MoE publication typeNot Eligible
Event102nd AACR Annual Meeting - Orlando, United States
Duration: 2 Apr 20116 Apr 2011
Conference number: 102

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Glioma
Biomarkers
Growth
Genes
Neoplasms
Astrocytoma
Cell Survival
Caspase 7
Oligodendroglioma
Data Mining
Gene Regulatory Networks
European Union
Finland
Glioblastoma
Brain Neoplasms
Caspase 3
Central Nervous System
Endothelial Cells
Cell Proliferation
Genome

Cite this

Haapa-Paananen, S., Kiviluoto, S., Waltari, M., Puputti, M., Mpindi, J., Kohonen, P., ... Kallioniemi, O. (2011). HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth. Cancer Research, 71(8 Suppl), [Abstract nr 3800]. https://doi.org/10.1158/1538-7445.AM2011-3800
Haapa-Paananen, Saija ; Kiviluoto, Santeri ; Waltari, Marika ; Puputti, Marjut ; Mpindi, John ; Kohonen, Pekka ; Tynninen, Olli ; Haapasalo, Hannu ; Joensuu, Heikki ; Perälä, Merja ; Kallioniemi, Olli. / HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth. In: Cancer Research. 2011 ; Vol. 71, No. 8 Suppl.
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abstract = "Malignant glioma is the most common brain tumor with 16,000 individuals diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9,783 Affymetrix samples from the GeneSapiens database (www.genesapiens.org) to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared to 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (Hairy and Enhancer of Split 6) emerged as one of the most glioma-specific genes. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8{\%}) out of the 339 glioma samples. HES6 was also expressed in endothelial cells in normal and glioma tissues. Recurrent grade 2 astrocytomas and grade 2-3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. Functional studies implied a critical role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and induction of Caspase 3/7 activity after HES6 silencing in A172 and LN405 cells. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc, and NF-?B transcriptional networks. We conclude that HES6 has a critical role in sustaining glioma cell growth, survival, migration and possibly angiogenesis. HES6 is a potential therapeutic target and biomarker for glioma. This work was supported by funding under the 6th FP of the European Union, Project RIGHT (LSHB-CT-2004-005276), and the Academy of Finland.",
author = "Saija Haapa-Paananen and Santeri Kiviluoto and Marika Waltari and Marjut Puputti and John Mpindi and Pekka Kohonen and Olli Tynninen and Hannu Haapasalo and Heikki Joensuu and Merja Per{\"a}l{\"a} and Olli Kallioniemi",
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Haapa-Paananen, S, Kiviluoto, S, Waltari, M, Puputti, M, Mpindi, J, Kohonen, P, Tynninen, O, Haapasalo, H, Joensuu, H, Perälä, M & Kallioniemi, O 2011, 'HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth', Cancer Research, vol. 71, no. 8 Suppl, Abstract nr 3800. https://doi.org/10.1158/1538-7445.AM2011-3800

HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth. / Haapa-Paananen, Saija; Kiviluoto, Santeri; Waltari, Marika; Puputti, Marjut; Mpindi, John; Kohonen, Pekka; Tynninen, Olli; Haapasalo, Hannu; Joensuu, Heikki; Perälä, Merja; Kallioniemi, Olli.

In: Cancer Research, Vol. 71, No. 8 Suppl, Abstract nr 3800, 2011.

Research output: Contribution to journalOther journal contributionScientificpeer-review

TY - JOUR

T1 - HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth

AU - Haapa-Paananen, Saija

AU - Kiviluoto, Santeri

AU - Waltari, Marika

AU - Puputti, Marjut

AU - Mpindi, John

AU - Kohonen, Pekka

AU - Tynninen, Olli

AU - Haapasalo, Hannu

AU - Joensuu, Heikki

AU - Perälä, Merja

AU - Kallioniemi, Olli

N1 - Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL

PY - 2011

Y1 - 2011

N2 - Malignant glioma is the most common brain tumor with 16,000 individuals diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9,783 Affymetrix samples from the GeneSapiens database (www.genesapiens.org) to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared to 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (Hairy and Enhancer of Split 6) emerged as one of the most glioma-specific genes. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was also expressed in endothelial cells in normal and glioma tissues. Recurrent grade 2 astrocytomas and grade 2-3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. Functional studies implied a critical role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and induction of Caspase 3/7 activity after HES6 silencing in A172 and LN405 cells. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc, and NF-?B transcriptional networks. We conclude that HES6 has a critical role in sustaining glioma cell growth, survival, migration and possibly angiogenesis. HES6 is a potential therapeutic target and biomarker for glioma. This work was supported by funding under the 6th FP of the European Union, Project RIGHT (LSHB-CT-2004-005276), and the Academy of Finland.

AB - Malignant glioma is the most common brain tumor with 16,000 individuals diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9,783 Affymetrix samples from the GeneSapiens database (www.genesapiens.org) to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared to 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (Hairy and Enhancer of Split 6) emerged as one of the most glioma-specific genes. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was also expressed in endothelial cells in normal and glioma tissues. Recurrent grade 2 astrocytomas and grade 2-3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. Functional studies implied a critical role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and induction of Caspase 3/7 activity after HES6 silencing in A172 and LN405 cells. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc, and NF-?B transcriptional networks. We conclude that HES6 has a critical role in sustaining glioma cell growth, survival, migration and possibly angiogenesis. HES6 is a potential therapeutic target and biomarker for glioma. This work was supported by funding under the 6th FP of the European Union, Project RIGHT (LSHB-CT-2004-005276), and the Academy of Finland.

U2 - 10.1158/1538-7445.AM2011-3800

DO - 10.1158/1538-7445.AM2011-3800

M3 - Other journal contribution

VL - 71

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 8 Suppl

M1 - Abstract nr 3800

ER -

Haapa-Paananen S, Kiviluoto S, Waltari M, Puputti M, Mpindi J, Kohonen P et al. HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth. Cancer Research. 2011;71(8 Suppl). Abstract nr 3800. https://doi.org/10.1158/1538-7445.AM2011-3800