PMID- 10366437
OWN - NLM
STAT- MEDLINE
DCOM- 19990702
LR  - 20071115
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 249
IP  - 2
DP  - 1999 Jun 15
TI  - Terminal differentiation of normal human oral keratinocytes is associated with 
      enhanced cellular TGF-beta and phospholipase C-gamma 1 levels and apoptotic cell 
      death.
PG  - 377-85
AB  - Subculture of primary normal human oral keratinocytes (NHOK) results in terminal 
      differentiation, leading to cell death. To investigate whether the 
      subculture-induced death of NHOK is due to apoptosis, we studied 
      transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, DNA 
      fragmentation, and expression of several apoptosis-associated genes from NHOK 
      with different passage numbers. We also determined the effect of transforming 
      growth factor beta1 (TGF-beta1) on the induction of apoptosis in NHOK. We were 
      able to subculture primary NHOK up to the fifth passage, at which point cells 
      showed morphological features of differentiation. Appearance of DNA fragmentation 
      concurrently occurred with an increase in the number of TUNEL-positive cells with 
      higher passage numbers. The level of cellular p53 proteins was gradually 
      decreased by the continued passage of cells, whereas the levels of intracellular 
      and secreted TGF-beta and phospholipase C-gamma1 (PLC-gamma1) were significantly 
      elevated by serial subculture. Exogenous TGF-beta1 also induced differentiation 
      and apoptosis of proliferating NHOK. These data indicate that terminal 
      differentiation of NHOK is associated with apoptosis, which is, in part, linked 
      to elevated cellular levels of TGF-beta and PLC-gamma1.
CI  - Copyright 1999 Academic Press.
FAU - Min, B M
AU  - Min BM
AD  - College of Dentistry, Seoul National University, Seoul, 110-749, Korea.
FAU - Woo, K M
AU  - Woo KM
FAU - Lee, G
AU  - Lee G
FAU - Park, N H
AU  - Park NH
LA  - eng
GR  - DE10598/DE/NIDCR NIH HHS/United States
GR  - DE11229/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Adult
MH  - Apoptosis/physiology
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/genetics
MH  - Gingiva/cytology
MH  - Humans
MH  - Isoenzymes/metabolism/*physiology
MH  - Keratinocytes/chemistry/*physiology
MH  - Phospholipase C gamma
MH  - RNA, Messenger/metabolism
MH  - Transforming Growth Factor beta/metabolism/*physiology
MH  - Tumor Suppressor Protein p53/genetics
MH  - Type C Phospholipases/metabolism/*physiology
EDAT- 1999/06/15 00:00
MHDA- 1999/06/15 00:01
CRDT- 1999/06/15 00:00
PHST- 1999/06/15 00:00 [pubmed]
PHST- 1999/06/15 00:01 [medline]
PHST- 1999/06/15 00:00 [entrez]
AID - S0014-4827(99)94489-0 [pii]
AID - 10.1006/excr.1999.4489 [doi]
PST - ppublish
SO  - Exp Cell Res. 1999 Jun 15;249(2):377-85. doi: 10.1006/excr.1999.4489.