Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells

Chun-liang Chen, Abbey Loy, Ling Cen, Christina Chan, Fu Chuan Hsieh, Gong Cheng, Bryant Wu, Stephen J. Qualman, Keita Kunisada, Keiko Yamauchi-Takihara, Jiayuh Lin

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Background: Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear. Methods: To examine whether Stat3 is activated in osteosarcomas, rhabdomyosarcomas and other soft-tissue sarcomas we analyzed sarcoma tissue microarray slides and sarcoma cell lines using immunohistochemistry and Western blot analysis, respectively, with a phospho-specific Stat3 antibody. To examine whether the activated Stat3 pathway is important for sarcoma cell growth and survival, adenovirus-mediated expression of a dominant-negative Stat3 (Y705F) and a small molecule inhibitor (termed STA-21) were used to inhibit constitutive Stat3 signaling in human sarcoma cell lines expressing elevated levels of Stat3 phosphorylation. Cell viability was determined by MTT assays and induction of apoptosis was analyzed by western blotting using antibodies that specifically recognize cleaved caspases-3, 8, and 9. Results: Stat3 phosphorylation is elevated in 19%(21/113) of osteosarcoma, 27% (17/64) of rhabdomyosarcoma, and 15% (22/151) of other soft-tissue sarcoma tissues as well as in sarcoma cell lines. Expression of the dominant-negative Stat3 and treatment of STA-21 inhibited cell viability and growth and induced apoptosis through caspases 3, 8 and 9 pathways in human sarcoma cell lines expressing elevated levels of phosphorylated Stat3. Conclusion: This study demonstrates that Stat3 phosphorylation is elevated in human rhabdomyo sarcoma, osteosarcomas and soft-tissue sarcomas. Furthermore, the activated Stat3 pathway is important for cell growth and survival of human sarcoma cells.

Original languageEnglish (US)
Article number111
JournalBMC Cancer
Volume7
DOIs
StatePublished - Jun 28 2007
Externally publishedYes

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STAT3 Transcription Factor
Rhabdomyosarcoma
Osteosarcoma
Sarcoma
Cell Survival
Growth
Cell Line
Caspase 9
Caspase 8
Phosphorylation
Caspase 3
Western Blotting
Phospho-Specific Antibodies
Apoptosis
Proto-Oncogenes
Adenoviridae
Carcinogenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells. / Chen, Chun-liang; Loy, Abbey; Cen, Ling; Chan, Christina; Hsieh, Fu Chuan; Cheng, Gong; Wu, Bryant; Qualman, Stephen J.; Kunisada, Keita; Yamauchi-Takihara, Keiko; Lin, Jiayuh.

In: BMC Cancer, Vol. 7, 111, 28.06.2007.

Research output: Contribution to journalArticle

Chen, C, Loy, A, Cen, L, Chan, C, Hsieh, FC, Cheng, G, Wu, B, Qualman, SJ, Kunisada, K, Yamauchi-Takihara, K & Lin, J 2007, 'Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells', BMC Cancer, vol. 7, 111. https://doi.org/10.1186/1471-2407-7-111
Chen, Chun-liang ; Loy, Abbey ; Cen, Ling ; Chan, Christina ; Hsieh, Fu Chuan ; Cheng, Gong ; Wu, Bryant ; Qualman, Stephen J. ; Kunisada, Keita ; Yamauchi-Takihara, Keiko ; Lin, Jiayuh. / Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells. In: BMC Cancer. 2007 ; Vol. 7.
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title = "Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells",
abstract = "Background: Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear. Methods: To examine whether Stat3 is activated in osteosarcomas, rhabdomyosarcomas and other soft-tissue sarcomas we analyzed sarcoma tissue microarray slides and sarcoma cell lines using immunohistochemistry and Western blot analysis, respectively, with a phospho-specific Stat3 antibody. To examine whether the activated Stat3 pathway is important for sarcoma cell growth and survival, adenovirus-mediated expression of a dominant-negative Stat3 (Y705F) and a small molecule inhibitor (termed STA-21) were used to inhibit constitutive Stat3 signaling in human sarcoma cell lines expressing elevated levels of Stat3 phosphorylation. Cell viability was determined by MTT assays and induction of apoptosis was analyzed by western blotting using antibodies that specifically recognize cleaved caspases-3, 8, and 9. Results: Stat3 phosphorylation is elevated in 19{\%}(21/113) of osteosarcoma, 27{\%} (17/64) of rhabdomyosarcoma, and 15{\%} (22/151) of other soft-tissue sarcoma tissues as well as in sarcoma cell lines. Expression of the dominant-negative Stat3 and treatment of STA-21 inhibited cell viability and growth and induced apoptosis through caspases 3, 8 and 9 pathways in human sarcoma cell lines expressing elevated levels of phosphorylated Stat3. Conclusion: This study demonstrates that Stat3 phosphorylation is elevated in human rhabdomyo sarcoma, osteosarcomas and soft-tissue sarcomas. Furthermore, the activated Stat3 pathway is important for cell growth and survival of human sarcoma cells.",
author = "Chun-liang Chen and Abbey Loy and Ling Cen and Christina Chan and Hsieh, {Fu Chuan} and Gong Cheng and Bryant Wu and Qualman, {Stephen J.} and Keita Kunisada and Keiko Yamauchi-Takihara and Jiayuh Lin",
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T1 - Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells

AU - Chen, Chun-liang

AU - Loy, Abbey

AU - Cen, Ling

AU - Chan, Christina

AU - Hsieh, Fu Chuan

AU - Cheng, Gong

AU - Wu, Bryant

AU - Qualman, Stephen J.

AU - Kunisada, Keita

AU - Yamauchi-Takihara, Keiko

AU - Lin, Jiayuh

PY - 2007/6/28

Y1 - 2007/6/28

N2 - Background: Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear. Methods: To examine whether Stat3 is activated in osteosarcomas, rhabdomyosarcomas and other soft-tissue sarcomas we analyzed sarcoma tissue microarray slides and sarcoma cell lines using immunohistochemistry and Western blot analysis, respectively, with a phospho-specific Stat3 antibody. To examine whether the activated Stat3 pathway is important for sarcoma cell growth and survival, adenovirus-mediated expression of a dominant-negative Stat3 (Y705F) and a small molecule inhibitor (termed STA-21) were used to inhibit constitutive Stat3 signaling in human sarcoma cell lines expressing elevated levels of Stat3 phosphorylation. Cell viability was determined by MTT assays and induction of apoptosis was analyzed by western blotting using antibodies that specifically recognize cleaved caspases-3, 8, and 9. Results: Stat3 phosphorylation is elevated in 19%(21/113) of osteosarcoma, 27% (17/64) of rhabdomyosarcoma, and 15% (22/151) of other soft-tissue sarcoma tissues as well as in sarcoma cell lines. Expression of the dominant-negative Stat3 and treatment of STA-21 inhibited cell viability and growth and induced apoptosis through caspases 3, 8 and 9 pathways in human sarcoma cell lines expressing elevated levels of phosphorylated Stat3. Conclusion: This study demonstrates that Stat3 phosphorylation is elevated in human rhabdomyo sarcoma, osteosarcomas and soft-tissue sarcomas. Furthermore, the activated Stat3 pathway is important for cell growth and survival of human sarcoma cells.

AB - Background: Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear. Methods: To examine whether Stat3 is activated in osteosarcomas, rhabdomyosarcomas and other soft-tissue sarcomas we analyzed sarcoma tissue microarray slides and sarcoma cell lines using immunohistochemistry and Western blot analysis, respectively, with a phospho-specific Stat3 antibody. To examine whether the activated Stat3 pathway is important for sarcoma cell growth and survival, adenovirus-mediated expression of a dominant-negative Stat3 (Y705F) and a small molecule inhibitor (termed STA-21) were used to inhibit constitutive Stat3 signaling in human sarcoma cell lines expressing elevated levels of Stat3 phosphorylation. Cell viability was determined by MTT assays and induction of apoptosis was analyzed by western blotting using antibodies that specifically recognize cleaved caspases-3, 8, and 9. Results: Stat3 phosphorylation is elevated in 19%(21/113) of osteosarcoma, 27% (17/64) of rhabdomyosarcoma, and 15% (22/151) of other soft-tissue sarcoma tissues as well as in sarcoma cell lines. Expression of the dominant-negative Stat3 and treatment of STA-21 inhibited cell viability and growth and induced apoptosis through caspases 3, 8 and 9 pathways in human sarcoma cell lines expressing elevated levels of phosphorylated Stat3. Conclusion: This study demonstrates that Stat3 phosphorylation is elevated in human rhabdomyo sarcoma, osteosarcomas and soft-tissue sarcomas. Furthermore, the activated Stat3 pathway is important for cell growth and survival of human sarcoma cells.

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