Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells. Surgery 2005 Dec;138(6):1137-42; discussion 1142
Date
12/20/2005Pubmed ID
16360401DOI
10.1016/j.surg.2005.05.027Scopus ID
2-s2.0-29144499299 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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.
Author List
Kunnimalaiyaan M, Yan S, Wong F, Zhang YW, Chen HMESH terms used to index this publication - Major topics in bold
Basic Helix-Loop-Helix Transcription FactorsCarcinoid Tumor
Cell Culture Techniques
Cell Line, Tumor
Cell Proliferation
Dose-Response Relationship, Drug
Doxycycline
Homeodomain Proteins
Humans
Lung Neoplasms
Receptor, Notch1
Transcription Factor HES-1
