RACK1 IS UP‐REGULATED IN ANGIOGENESIS AND HUMAN CARCINOMAS

• Published in: The FASEB journal 2000-12, Vol.14 (15), p.2549-2558
• Main Authors: Berns, Hartmut, Humar, Rok, Hengerer, Bastian, Kiefer, Fabrice N., Battegay, Edouard J.
• Format: Article
• Language: English
• Subjects: angiogenic process; Animals; Base Sequence; cancer; Carcinoma - genetics; Cattle; Cloning, Molecular; DNA, Complementary - genetics; endothelium; Endothelium, Vascular - metabolism; Estrus - physiology; Female; GTP-Binding Proteins; Humans; Molecular Sequence Data; Neoplasm Proteins - genetics; Neovascularization, Pathologic - genetics; Neovascularization, Physiologic - genetics; RACK1 protein; receptor for activated PKCβ; Receptors for Activated C Kinase; Receptors, Cell Surface - genetics; RNA, Messenger - isolation & purification; RNA, Neoplasm - isolation & purification; Sequence Homology, Nucleic Acid; signaling; Up-Regulation
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.99-1038com

ABSTRACT 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 β (PKCβ), 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. PKCβ plays an important role in angiogenesis and cancer growth. Our data suggest that downstream signaling of PKCβ 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. The FASEB J. 14, 2549–2558 (2000)