Amyloid beta protein precursor is involved in the growth of human colon carcinoma cell in vitro and in vivo.
Amyloid beta protein precursor (APP) is a membrane-bound protein ubiquitously expressed in a variety of types of cells. However, its biological functions remain largely uncertain, particularly in non-neural cells and tumors. Our previous studies revealed that a secreted form of APP having a Kunitz-type inhibitor domain is a major serine proteinase inhibitor secreted by human colon carcinoma cells. In our study, we used an antisense RNA strategy to selectively inhibit the expression of APP in the human colon carcinoma cell line SW837. A vector capable of expressing an antisense mRNA complementary to 911 bases of the 5' end of APP mRNA was transfected into SW837 cells. After selection, 2 stably transfected antisense clones were obtained in which both the APP protein and mRNA were significantly suppressed. The proliferative potential and colony-forming efficiency of the antisense clones in vitro were markedly suppressed compared with the parent and mock-transfected clones. The addition of the conditioned medium of parent cells or purified secretory APP enabled these antisense effects to be overcome in vitro. The suppressed growth was also observed in vivo when the cells were injected subcutaneously into nude mice. Histologically, formation of tubular structures appeared to be suppressed in the antisense clones in vivo. These observations suggest potentially important roles of APP in cellular proliferation and differentiation of colon carcinoma cells.
Second Department of Pathology, Miyazaki Medical College, Miyazaki, Japan.
J Y
JY
Meng
H
H
Kataoka
H
H
Itoh
M
M
Koono
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D003110:Colonic Neoplasms / Q000473:pathology*; D017077:Culture Media, Conditioned; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D017077:Culture Media, Conditioned; D019394:Ki-67 Antigen; D016372:RNA, Antisense; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases