Effect of apoptogenic stimuli on colon carcinoma cell lines with a different c-myc expression level.
We have recently demonstrated that a high c-myc endogenous amplification level confers an apoptosis-prone phenotype to serum-deprived colon carcinoma SW613-S cells. The aim of this study was to gain new insights into the features of c-myc-dependent apoptosis, by extending our analysis to different apoptogenic stimuli. The study was carried out on clones, derived from the human colon carcinoma SW613-S cell line, which harbor different levels of endogenous c-myc amplification, and on isogenic cell lines with an enforced c-myc overexpression. Our results indicate that cells with endogenous or transfected exogenous c-myc overexpression (SW613-12A1 and -2G1mycP2Tu1 cell lines, respectively), activate the apoptotic machinery in response to the treatment with etoposide, doxorubicin and vitamin D3, which induce apoptosis through the death receptor Fas. The low levels of c-myc expression present in SW613-B3 and -B3mycC5, seem to be unable to activate Fas-mediated apoptosis, thus suggesting that only a high c-myc expression can bypass the lack of Fas receptor. Apoptosis induction mediated by DNA damage and long-term culture was independent of c-myc expression. A pathway of apoptosis characterized by the activation of the enzyme L-DNase II, was observed in both 12A1 and B3 cell lines.
Istituto di Genetica Molecolare CNR, I-27100 Pavia, Italy.
Chiara
C
Gorrini
Maddalena
M
Donzelli
Alicia
A
Torriglia
Rosanna
R
Supino
Olivier
O
Brison
Rosa
R
Bernardi
Claudia
C
Negri
Marco
M
Denegri
Marie-France
MF
Counis
G Nadia
GN
Ranzani
A Ivana
AI
Scovassi
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001761:Bleomycin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D014162:Transfection; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; D019014:fas Receptor; D001761:Bleomycin; D002762:Cholecalciferol; D005047:Etoposide; D004317:Doxorubicin; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II