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HES1 Expression Uncoupled From Notch in Ewing's Sarcoma

Notch receptors and effector HES1 expression restricted to outside of the cell nuclei

TUESDAY, July 26 (HealthDay News) -- HES1 expression is not always associated with Notch activity in Ewing's sarcoma family of tumors (ESFT), according to a study published online July 15 in The Journal of Pathology.

Idriss M. Bennani-Baiti, Ph.D., from the Children's Cancer Research Institute in Vienna, Austria, and colleagues investigated the Notch pathway in ESFT by profiling gene expression via meta-analysis of samples from 96 patients, and immunohistochemistry of 24 samples from patients with ESFT.

The investigators found that Notch receptors were highly expressed, but were absent from the cell nuclei, suggesting that Notch was not active. Cell nuclei stained for active notch receptors in colon adenocarcinoma, hepatocarcinoma, and pancreatic carcinomas. In the majority of ESFT, high expression of the Notch effector HES1 was also limited to outside of the nucleus, and analysis of gene targets indicated that HES1 was transcriptionally inactive. HES1 expression in ESFT cells was not affected by forced activation, or pharmacological or genetic blocking of Notch. In functional studies from ESFT cell lines, Notch was confirmed as switched off. Experimental activation of Notch in ESFT cell lines blocked cell proliferation and reduced their clonogenic potential in soft agar.

"These findings indicate that HES1 expression may not always reflect Notch activity, and that Notch activation may not always lead to HES1 activation," the authors write.

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