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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Article info
Publication history
Madison, Wis
Footnotes
Presented at the 26th Annual Meeting of the American Association of Endocrine Surgeons, Cancun, Mexico, April 3-5, 2005.
Supported in part by an American Surgical Association Foundation grant, an American College of Surgeons George Clowes Memorial Award, National Institutes of Health grants R21-DK063015, R21-DK064735, R21-DK066169, and an American Cancer Society Research Scholars Grant.
Identification
Copyright
© 2005 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
