Inhibition of CD95-mediated apoptosis through beta 1 integrin in the HSG epithelial cell line.
The HSG cell line serves as a model for salivary gland epithelial progenitor cell differentiation. In order for a progenitor cell to differentiate, the cell must maintain viability within its niche. Studies were designed to elucidate the mechanism for integrin-mediated HSG cell survival. HSG cells, grown on Matrigel, were resistant to CD95-mediated apoptosis. Western blot analysis showed that Matrigel induced the expression of bcl-2, bcl-xL, p63, and DeltaNp63. This induction occurred by as early as 2 hrs and remained for 24 hrs. CD95-mediated apoptosis resistance was dependent, however, upon the expression of the bcl-2 family. Furthermore, Matrigel induced bcl-2 family expression was dependent on the transactivation of the EGF receptor pathway since PD98059 and AG1478 inhibited Matrigel induced bcl-2 family expression and caused HSG cells to be sensitive to CD95-mediated apoptosis. Activation of the EGF receptor pathway, by itself, however, was not sufficient to inhibit apoptosis. Blocking antibody showed that bcl-2 family expression was mediated through beta1 integrin. These studies show that salivary progenitor epithelial cell survival is integrin dependent and involves the transactivation of the EGF receptor pathway.
Dang
Howard
H
Department of Community Dentistry, The University of Texas Health Science Center at San Antonio, Texas 78229-3900, USA. dang@uthscsa.edu
Dehghan
Parastou Lizeth
PL
Goodwiler
Kai
K
Chen
Shuo
S
Zardeneta
Gustavo
G
Zhang
Bin-Xian
BX
Yeh
Chih-Ko
CK
D017209:Apoptosis / Q000502:physiology*; D001578:Benzopyrans / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D003094:Collagen / Q000502:physiology; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D039641:Integrin beta Chains / Q000502:physiology*; D007797:Laminin / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011509:Proteoglycans / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism* / Q000502:physiology
D001578:Benzopyrans; C081876:CKAP4 protein, human; D004338:Drug Combinations; D005419:Flavonoids; D039641:Integrin beta Chains; D007797:Laminin; D008565:Membrane Proteins; D009570:Nitriles; D009842:Oligopeptides; D011509:Proteoglycans; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D019014:fas Receptor; C059485:matrigel; D004815:Epidermal Growth Factor; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one