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Two- and Three-dimensional Cell Structures Govern Epidermal Growth Factor Survival Function in Human Bladder Carcinoma Cell Lines¹

URA INRA-DGER d'Immunopathologie Cellulaire et Moléculaire, Ecole Nationale Vétérinaire, 94704 Maisons Alfort cedex [V. D., F. F., V. L., M. B., D. L. R., D. L., I. S-C.], and Institut Curie, 26 rue d'Ulm, 75005 Paris [M-F. P.], France

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 , enhanced the apoptosis due to serum starvation on cells cultured as monolayers. Conversely, EGF and transforming growth factor 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.

¹ Supported by the Institut National de la Recherche Agronomique.

² Present address: Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75006 Paris, France.

³ To whom requests for reprints should be addressed.

Received 3/18/97. Accepted 7/ 2/97.

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