Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells

Muthusamy Kunnimalaiyaan, Sonia Yan, Francis Wong, Yi Wei Zhang, Herbert Chen, B. Skogseid, Alan P B Dackiw, Electron Kebebew

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Abstract

Background. The Notch1-signaling pathway has been shown to regulate the differentiation and growth of carcinoid tumor cells. However, the molecules that mediate Notch1 signaling, as well as their potential roles in regulating the growth of carcinoid tumors, have not been characterized. We and others have shown previously that the transcription factor Hairy Enhancer of Split-1 (HES-1) is upregulated in response to Notch1 signaling, demonstrating that it is a Notch1 effector. We hypothesized that HES-1 may be the essential downstream factor in Notch1-mediated growth regulation of carcinoid tumors. Methods. H727 carcinoid tumor cells were transduced stably with a doxycycline-inducible HES-1 construct, creating H727-HES-1 cells. H727-TRE (vector-only control) and H727-HES-1 cells were then treated with varying concentrations of doxycycline to achieve increasing levels of HES-1 protein expression. Cell proliferation was determined with the use of a cell viability assay. Results. Treatment of H727-HES-1 cells with increasing dosages of doxycycline resulted in dose-dependent increases in HES-1 protein by Western blot analysis. Importantly, induction of HES-1 in carcinoid tumor cells led to suppression of tumor cellular proliferation. Moreover, the degree of carcinoid growth inhibition appeared to be proportional to the level of HES-1 induction. Conclusions. HES-1 alone can regulate the growth of carcinoid tumor cells. Furthermore, these results suggest that HES-1 may be the critical downstream effector in the Notch1-signaling pathway.

Original languageEnglish (US)
Pages (from-to)1137-1142
Number of pages6
JournalSurgery
Volume138
Issue number6
DOIs
StatePublished - Dec 2005

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Carcinoid Tumor
Growth
Doxycycline
Cell Proliferation
Cell Survival
Transcription Factors
Western Blotting
Neoplasms

ASJC Scopus subject areas

  • Surgery

Cite this

Kunnimalaiyaan, M., Yan, S., Wong, F., Zhang, Y. W., Chen, H., Skogseid, B., ... Kebebew, E. (2005). Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells. Surgery, 138(6), 1137-1142. https://doi.org/10.1016/j.surg.2005.05.027

Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells. / Kunnimalaiyaan, Muthusamy; Yan, Sonia; Wong, Francis; Zhang, Yi Wei; Chen, Herbert; Skogseid, B.; Dackiw, Alan P B; Kebebew, Electron.

In: Surgery, Vol. 138, No. 6, 12.2005, p. 1137-1142.

Research output: Contribution to journalArticle

Kunnimalaiyaan, M, Yan, S, Wong, F, Zhang, YW, Chen, H, Skogseid, B, Dackiw, APB & Kebebew, E 2005, 'Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells', Surgery, vol. 138, no. 6, pp. 1137-1142. https://doi.org/10.1016/j.surg.2005.05.027
Kunnimalaiyaan M, Yan S, Wong F, Zhang YW, Chen H, Skogseid B et al. Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells. Surgery. 2005 Dec;138(6):1137-1142. https://doi.org/10.1016/j.surg.2005.05.027
Kunnimalaiyaan, Muthusamy ; Yan, Sonia ; Wong, Francis ; Zhang, Yi Wei ; Chen, Herbert ; Skogseid, B. ; Dackiw, Alan P B ; Kebebew, Electron. / Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells. In: Surgery. 2005 ; Vol. 138, No. 6. pp. 1137-1142.
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abstract = "Background. The Notch1-signaling pathway has been shown to regulate the differentiation and growth of carcinoid tumor cells. However, the molecules that mediate Notch1 signaling, as well as their potential roles in regulating the growth of carcinoid tumors, have not been characterized. We and others have shown previously that the transcription factor Hairy Enhancer of Split-1 (HES-1) is upregulated in response to Notch1 signaling, demonstrating that it is a Notch1 effector. We hypothesized that HES-1 may be the essential downstream factor in Notch1-mediated growth regulation of carcinoid tumors. Methods. H727 carcinoid tumor cells were transduced stably with a doxycycline-inducible HES-1 construct, creating H727-HES-1 cells. H727-TRE (vector-only control) and H727-HES-1 cells were then treated with varying concentrations of doxycycline to achieve increasing levels of HES-1 protein expression. Cell proliferation was determined with the use of a cell viability assay. Results. Treatment of H727-HES-1 cells with increasing dosages of doxycycline resulted in dose-dependent increases in HES-1 protein by Western blot analysis. Importantly, induction of HES-1 in carcinoid tumor cells led to suppression of tumor cellular proliferation. Moreover, the degree of carcinoid growth inhibition appeared to be proportional to the level of HES-1 induction. Conclusions. HES-1 alone can regulate the growth of carcinoid tumor cells. Furthermore, these results suggest that HES-1 may be the critical downstream effector in the Notch1-signaling pathway.",
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AU - Wong, Francis

AU - Zhang, Yi Wei

AU - Chen, Herbert

AU - Skogseid, B.

AU - Dackiw, Alan P B

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N2 - Background. The Notch1-signaling pathway has been shown to regulate the differentiation and growth of carcinoid tumor cells. However, the molecules that mediate Notch1 signaling, as well as their potential roles in regulating the growth of carcinoid tumors, have not been characterized. We and others have shown previously that the transcription factor Hairy Enhancer of Split-1 (HES-1) is upregulated in response to Notch1 signaling, demonstrating that it is a Notch1 effector. We hypothesized that HES-1 may be the essential downstream factor in Notch1-mediated growth regulation of carcinoid tumors. Methods. H727 carcinoid tumor cells were transduced stably with a doxycycline-inducible HES-1 construct, creating H727-HES-1 cells. H727-TRE (vector-only control) and H727-HES-1 cells were then treated with varying concentrations of doxycycline to achieve increasing levels of HES-1 protein expression. Cell proliferation was determined with the use of a cell viability assay. Results. Treatment of H727-HES-1 cells with increasing dosages of doxycycline resulted in dose-dependent increases in HES-1 protein by Western blot analysis. Importantly, induction of HES-1 in carcinoid tumor cells led to suppression of tumor cellular proliferation. Moreover, the degree of carcinoid growth inhibition appeared to be proportional to the level of HES-1 induction. Conclusions. HES-1 alone can regulate the growth of carcinoid tumor cells. Furthermore, these results suggest that HES-1 may be the critical downstream effector in the Notch1-signaling pathway.

AB - Background. The Notch1-signaling pathway has been shown to regulate the differentiation and growth of carcinoid tumor cells. However, the molecules that mediate Notch1 signaling, as well as their potential roles in regulating the growth of carcinoid tumors, have not been characterized. We and others have shown previously that the transcription factor Hairy Enhancer of Split-1 (HES-1) is upregulated in response to Notch1 signaling, demonstrating that it is a Notch1 effector. We hypothesized that HES-1 may be the essential downstream factor in Notch1-mediated growth regulation of carcinoid tumors. Methods. H727 carcinoid tumor cells were transduced stably with a doxycycline-inducible HES-1 construct, creating H727-HES-1 cells. H727-TRE (vector-only control) and H727-HES-1 cells were then treated with varying concentrations of doxycycline to achieve increasing levels of HES-1 protein expression. Cell proliferation was determined with the use of a cell viability assay. Results. Treatment of H727-HES-1 cells with increasing dosages of doxycycline resulted in dose-dependent increases in HES-1 protein by Western blot analysis. Importantly, induction of HES-1 in carcinoid tumor cells led to suppression of tumor cellular proliferation. Moreover, the degree of carcinoid growth inhibition appeared to be proportional to the level of HES-1 induction. Conclusions. HES-1 alone can regulate the growth of carcinoid tumor cells. Furthermore, these results suggest that HES-1 may be the critical downstream effector in the Notch1-signaling pathway.

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