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Within 24 h, cell division was completely inhibited, suggesting the cells had entered a quiescent state. Continued incubation n the presence of phorbol esters resulted in the resumption of thymidine incorporation and cell division, but this coincided with only a partial down\u2010regulation of PKC activity. Seventy two hours of treatment was required to obtain down\u2010regulation of greater than 80% of the PKC activity, but reversal of the inhib tory 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\u2010state levels of c\u2010myc and transforming growth factor \u03b2<jats:sub>1<\/jats:sub> (TGF\u2010\u03b2<jats:sub>1<\/jats:sub>) messages increased only after 3 h of phorbol ester treatment and returned to normal levels after 24 h. C\u2010fos, 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 downregulation 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.<\/jats:p>","DOI":"10.1002\/jcp.1041450225","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T09:28:24Z","timestamp":1109410104000},"page":"381-389","source":"Crossref","is-referenced-by-count":37,"title":["Partial down\u2010regulation of protein kinase C reverses the growth inhibitory effect of phorbol esters on HepG2 cells"],"prefix":"10.1002","volume":"145","author":[{"given":"Vincent","family":"Duronio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian E.","family":"Huber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.9.2822"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.6.1408"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2360227"},{"key":"e_1_2_1_5_1","first-page":"1","article-title":"Protein kinase C as the receptor for the phorbol ester tumor promoters: Sixth Rhoads Memorial Award lecture","volume":"48","author":"Blumberg P. 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