PMID- 1978839
OWN - NLM
STAT- MEDLINE
DCOM- 19910108
LR  - 20131121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 145
IP  - 2
DP  - 1990 Nov
TI  - Partial down-regulation of protein kinase C reverses the growth inhibitory effect 
      of phorbol esters on HepG2 cells.
PG  - 381-9
AB  - Phorbol ester treatment of HepG2, a human tumorigenic cell line, caused rapid 
      morphological changes characterized by a flattening and spreading of the cells 
      that coincided with a rapid inhibition of thymidine incorporation. Within 24 h, 
      cell division was completely inhibited, suggesting the cells had entered a 
      quiescent state. Continued incubation in the presence of phorbol esters resulted 
      in the resumption of thymidine incorporation and cell division, but this 
      coincided with only a partial down-regulation of PKC activity. Seventy-two hours 
      of treatment was required to obtain down-regulation of greater than 80% of the 
      PKC activity, but reversal of the inhibitory effects occurred between 24 and 48 h 
      after the addition of phorbol esters, when a large proportion of the PKC activity 
      was still present. Northern blot analysis of a number of transcripts showed that 
      the steady-state levels of c-myc and transforming growth factor beta 1 (TGF-beta 
      1) messages increased only after 3 h of phorbol ester treatment and returned to 
      normal levels after 24 h. C-fos, albumin, and alphafetoprotein messages were not 
      affected, suggesting the differentiation state of the cells was not altered. 
      Therefore, phorbol ester activation of PKC causes an inhibition of HepG2 cell 
      growth initially, but this is unlike the promotion of differentiation seen in 
      other systems. Partial down-regulation of PKC activity causes a reversal of the 
      growth inhibition and the cells return to a normal growth rate. This effect is 
      also clearly different from systems in which phorbol esters have been shown to 
      have a mitogenic effect on cells.
FAU - Duronio, V
AU  - Duronio V
AD  - Biomedical Research Centre, University of British Columbia, Vancouver.
FAU - Huber, B E
AU  - Huber BE
FAU - Jacobs, S
AU  - Jacobs S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Phorbol Esters)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Somatomedin)
RN  - 0 (Transforming Growth Factor beta)
RN  - 24937-83-5 (Poly A)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Carcinoma, Hepatocellular
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Down-Regulation
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Liver/cytology/*metabolism
MH  - Liver Neoplasms
MH  - Phenotype
MH  - Phorbol Esters/*pharmacology
MH  - Poly A/biosynthesis
MH  - Protein Kinase C/*physiology
MH  - Proto-Oncogene Proteins c-myc/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Receptor, Insulin/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Somatomedin
MH  - Thymidine/metabolism
MH  - Time Factors
MH  - Transforming Growth Factor beta/genetics
MH  - Tumor Cells, Cultured
EDAT- 1990/11/01 00:00
MHDA- 1990/11/01 00:01
CRDT- 1990/11/01 00:00
PHST- 1990/11/01 00:00 [pubmed]
PHST- 1990/11/01 00:01 [medline]
PHST- 1990/11/01 00:00 [entrez]
AID - 10.1002/jcp.1041450225 [doi]
PST - ppublish
SO  - J Cell Physiol. 1990 Nov;145(2):381-9. doi: 10.1002/jcp.1041450225.