Two- and three-dimensional cell structures govern epidermal growth factor survival function in human bladder carcinoma cell lines.
Human bladder carcinomas often express high levels of the epidermal growth factor (EGF) receptor. In three human bladder carcinoma cell lines (OBR, T24, and 647V), we show that two EGF receptor ligands, namely EGF and transforming growth factor alpha, enhanced the apoptosis due to serum starvation on cells cultured as monolayers. Conversely, EGF and transforming growth factor alpha prevented apoptosis when the same serum-starved cells were cultured as three-dimensional spheroids. Both stimulation and inhibition of apoptosis by EGF were associated with p21 WAF1/CIP1 overexpression. In 647V spheroids, EGF protection against radiation-induced apoptosis was negated by genistein and tyrphostin AG1478, suggesting that blockade of the EGF signal transduction in patients with bladder cancer may improve the radiotherapy efficacy.
Dangles
V
V
URA INRA-DGER d'Immunopathologie Cellulaire et Moléculaire, Ecole Nationale Vétérinaire, Maisons Alfort, France.
Féménia
F
F
Lainé
V
V
Berthelemy
M
M
Le Rhun
D
D
Poupon
M F
MF
Levy
D
D
Schwartz-Cornil
I
I
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020032:Tyrphostins; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
C493956:CDKN1A protein, human; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007529:Isoflavones; D009363:Neoplasm Proteins; D009570:Nitriles; D011799:Quinazolines; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases