PDGF AA as mediator in nicotine-dependent carcinogenesis.
Effect of nicotine on PDGF AA and PDGF BB interaction with cervical cancer SiHa cells was tested. [125I]PDGF AA was internalized by cells and accumulated in the cytoplasm and nucleus (chromatin). In the absence of nicotine, maximal accumulation of [125I]PDGF AA inside the cells occurred after 1 day of incubation, which was followed by a progressive degradation of the growth factor during the next 2, 3 and 5 days of cell exposure. In the presence or 0.001 or 0.01% nicotine, accumulation of [125I]PDGF AA was slightly higher than in the absence of nicotine, and maximal accumulation occurred after 2 days or incubation. In the presence of 0.1 % nicotine, maximal accumulation occurred after 5 days of incubation and was 20 and 14 times higher in the cytoplasm and chromatin, respectively. Nicotine-postponed degradation and increased nuclear accumulation of PDGF AA resulted in activation of RNA synthesis and cell proliferation. PDGF BB, which was not internalized by cells did not respond to nicotine treatment. The proposed mechanism of nicotine-PDGF AA co-carcinogenesis may involve inhibition of growth factor degradation at the lysosomal level and an increased chromatin accumulation of the non-degraded PDGF.
Rakowicz-Szulczynska
E M
EM
Department of Obstetrics, University of Nebraska Medical Center, Eppley Cancer Center, Omaha 68198-3255, USA.
McIntosh
D G
DG
Perry
M
M
Smith
M L
ML
D000077214:Becaplermin; D001692:Biological Transport / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D009538:Nicotine / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms
D002273:Carcinogens; D002843:Chromatin; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012334:RNA, Neoplasm; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D009538:Nicotine