TY - JOUR
T1 - Interferon-β induces S phase slowing via up-regulated expression of PML in squamous carcinoma cells
AU - Vannucchi, Serena
AU - Percario, Zulema A.
AU - Chiantore, Maria V.
AU - Matarrese, Paola
AU - Chelbi-Alix, Mounira K.
AU - Fagioli, Marta
AU - Pelicci, Pier Giuseppe
AU - Malorni, Walter
AU - Fiorucci, Gianna
AU - Romeo, Giovanna
AU - Affabris, Elisabetta
PY - 2000/10/19
Y1 - 2000/10/19
N2 - Type I Interferon (IFN) and all-trans retinoic acid (RA) inhibit cell proliferation of squamous carcinoma cell lines (SCC). Examinations of growth-affected cell populations show that SCC lines ME-180 and SiHa treated with IFN-β undergo a specific slower progression through the S phase that seems to trigger cellular death. In combination treatment RA potentiates IFN-β effect in SCC ME-180 but not in SiHa cell line, partially resistant to RA antiproliferative action. RA added as single agent affect cell proliferation differently by inducing a slight G1 accumulation. The IFN-β-induced S phase lengthening parallels the increased expression of PML, a nuclear phosphoprotein specifically up-regulated at transcriptional level by IFN, whose overexpression induces cell growth inhibition and tumor suppression. We report that PML up-regulation may account for the alteration of cell cycle progression induced by IFN-β in SCC by infecting cells with PML-PINCO recombinant retrovirus carrying the PML-3 cDNA under the control of the 5' LTR. In fact PML overexpression reproduces the IFN-β-induced S phase lengthening. These findings provide important insight into the mechanism of tumor suppressing function of PML and could allow PML to be included in the pathways responsible for IFN-induced cell growth suppression.
AB - Type I Interferon (IFN) and all-trans retinoic acid (RA) inhibit cell proliferation of squamous carcinoma cell lines (SCC). Examinations of growth-affected cell populations show that SCC lines ME-180 and SiHa treated with IFN-β undergo a specific slower progression through the S phase that seems to trigger cellular death. In combination treatment RA potentiates IFN-β effect in SCC ME-180 but not in SiHa cell line, partially resistant to RA antiproliferative action. RA added as single agent affect cell proliferation differently by inducing a slight G1 accumulation. The IFN-β-induced S phase lengthening parallels the increased expression of PML, a nuclear phosphoprotein specifically up-regulated at transcriptional level by IFN, whose overexpression induces cell growth inhibition and tumor suppression. We report that PML up-regulation may account for the alteration of cell cycle progression induced by IFN-β in SCC by infecting cells with PML-PINCO recombinant retrovirus carrying the PML-3 cDNA under the control of the 5' LTR. In fact PML overexpression reproduces the IFN-β-induced S phase lengthening. These findings provide important insight into the mechanism of tumor suppressing function of PML and could allow PML to be included in the pathways responsible for IFN-induced cell growth suppression.
KW - All-trans retinoic acid
KW - Cell cycle
KW - Interferon
KW - PML
KW - Squamous carcinoma cells
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UR - http://www.scopus.com/inward/citedby.url?scp=0034687293&partnerID=8YFLogxK
M3 - Article
C2 - 11042692
AN - SCOPUS:0034687293
VL - 19
SP - 5041
EP - 5053
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 44
ER -