Down-regulation of cellular proto-oncogenes during inhibition of rat parotid acinar cell proliferation.
The role of cell surface galactosyltransferase in mediating isoproterenol-induced parotid gland hypertrophy and hyperplasia was examined in rat parotid gland acinar cells. Introduction of the transferase modifier, alpha-lactalbumin, or galactosyltransferase-associated kinase inhibitor trifluoperazine, into beta-agonist-treated rats prevented acinar cell proliferation as determined by [3H]thymidine incorporation after 96 h of treatment. However, [3H]thymidine incorporation into DNA after 24 h of treatment, with injection of a combination of isoproterenol/alpha-lactalbumin or isoproterenol/trifluoperazine, was similar to injections of isoproterenol alone; suggesting that acinar cells could be stimulated to undergo a single round of DNA synthesis. Northern blot analysis of myc and fos expression followed a similar pattern of down-regulation to control levels after 96 h but not after 24 h. Hybridization with erb B showed little change with proliferation, confirming previous observations on protein levels of the EGF-receptor in acinar cells. Western blot analysis of nuclear protein expression of myc revealed that isoproterenol caused an increase in a 62-kDa protein which was again down-regulated with inhibition of cell proliferation. Analysis of protein levels of Rb110 protein showed no change in protein level in the nucleus with cell proliferation, but did show an associated increase in protein phosphorylation in response to growth stimulation.
Lee
S W
SW
Department of Oral Biology, University of Florida, Gainesville.
Purushotham
K R
KR
Littlewood
T
T
Evan
G
G
Zelles
T
T
Blazsek
J
J
Nakagawa
Y
Y
Humphreys-Beher
M G
MG
D000818:Animals; D002455:Cell Division; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression; D007545:Isoproterenol / Q000494:pharmacology; D010306:Parotid Gland / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D016160:Retinoblastoma Protein / Q000032:analysis; D015398:Signal Transduction
D010750:Phosphoproteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D005700:Galactosyltransferases; D007545:Isoproterenol