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(The FASEB Journal. 2000;14:2549-2558.)
© 2000 FASEB

RACK1 is up-regulated in angiogenesis and human carcinomas 1

HARTMUT BERNS*, ROK HUMAR*, BASTIAN HENGERER§, FABRICE N. KIEFER* and EDOUARD J. BATTEGAY*,{dagger}2

* Cardiovascular Research Group, Department of Research, and
{dagger} Medical University Outpatient Division, University Hospital, 4031 Basel, Switzerland; and
§ Nervous System Therapeutic Area, Novartis, 4002 Basel, Switzerland

2Correspondence: Head Laboratory of Vascular Biology and Hypertension Clinic, Department of Research and Medical Outpatient Division, University Hospital, Petersgraben 3, CH-4031 Basel, Switzerland. E-mail: ebattegay{at}uhbs.ch

Angiogenesis is crucial for many biological and pathological processes including the ovarian cycle and tumor growth. To identify molecules relevant for angiogenesis, we performed mRNA fingerprinting and subsequent Northern blot analysis using bovine cord-forming vs. monolayer-forming endothelial cells (EC) in vitro and staged bovine corpora lutea in vivo. We detected the receptor for activated C kinase 1 (RACK1), the specific receptor for activated protein kinase C ß (PKCß), to be up-regulated in bovine cord-forming EC in vitro and in angiogenically active stages of bovine corpora lutea in vivo. Thereafter we established and determined the complete bovine RACK1 cDNA sequence. RACK1 was massively induced in subconfluent vs. contact-inhibited bovine EC, during angiogenesis in vitro, active phases of the murine ovarian cycle, human tumor angiogenesis, and in cancer cells in vivo as assessed by quantitative PCR and in situ hybridization. RACK1 transcripts were localized to proliferating EC in vitro and the endothelium of tumor neovascularizations in vivo by in situ hybridization. PKCß plays an important role in angiogenesis and cancer growth. Our data suggest that downstream signaling of PKCß in angiogenically active vs. inactive tissues and endothelium is affected by the availability of RACK1.—Berns, H., Humar, R., Hengerer, B., Kiefer, F. N., Battegay, E. J. RACK1 is up-regulated in angiogenesis and human carcinomas.


Key Words: receptor for activated PKCß • signaling • angiogenic process • endothelium • cancer




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