RACK1 is up-regulated in angiogenesis and human carcinomas.
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 beta (PKC beta), 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. PKC beta plays an important role in angiogenesis and cancer growth. Our data suggest that downstream signaling of PKC beta in angiogenically active vs. inactive tissues and endothelium is affected by the availability of RACK1.
Berns
H
H
Cardiovascular Research Group, Department of Research, University Hospital, basel, Switzerland.
Humar
R
R
Hengerer
B
B
Kiefer
F N
FN
Battegay
E J
EJ
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics*; D002417:Cattle; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D004971:Estrus / Q000502:physiology; D005260:Female; D019204:GTP-Binding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D012333:RNA, Messenger / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000302:isolation & purification; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D015854:Up-Regulation
D018076:DNA, Complementary; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins