Rcl, a Novel Breast Cancer Oncoprotein?
Final rept. 7 Jul 2003-6 Jul 2004
MAYO CLINIC ROCHESTER MN MAYO CLINIC COLL OF MEDICINE
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Rcl is an undefined protein whose expression can be induced by the oncoproteins c-Myc and HER2Neu, both of which are heavily implicated in breast tumorigenesis. As such, Rcl may be an important downstream effector of c-Myc and HER2Neu in breast cancer. To prove this hypothesis, we pursued three lines of research i We studied the potential co- overexpression of Rcl, c-Myc and HER2Neu in human breast tumor specimens and found Rcl to be overexpressed in one-third of all cases, but seemingly independent of HER2Neu and c- Myc overexpression. This suggests that Rcl is an oncogene contributing to cancer. ii We wished to assess the importance of Rcl for the phenotypic changes observable in tumor cells. To this end, we attempted to knock-down Rcl expression by RNA interference and study the resultant phenotypic changes in tumor cells. However, these experiments could not yet be performed due to our inability to generate effective Rcl siRNA. iii To unravel Rds mode of action, potential interaction partners have been identified by a yeast two-hybrid screen and a procedure has been developed to isolate Rcl-containg protein complexes amenable for mass spectrometric identification. Thus, the foundation for the identification of Rcl interaction partners has been established.
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