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See detailRegulation by androgens of EGF receptor family members in prostate cancer cells
Pignon, Jean-Christophe; Delacroix, Laurence ULg; Waltregny, David ULg et al

in Proceedings of the American Association for Cancer Research (2006)

After an initial positive response to anti-androgen treatment, prostate cancer (PCa) cells usually become hormone-refractory in spite of their persistent expression of the androgen receptor (AR ... [more ▼]

After an initial positive response to anti-androgen treatment, prostate cancer (PCa) cells usually become hormone-refractory in spite of their persistent expression of the androgen receptor (AR). Overexpression of tyrosine kinase receptors in androgen-deprived PCa cells, such as those of the EGF receptor (EGFR) family, may be responsible for AR activation and growth of androgen-deprived tumours. Our goal is to understand the control of the expression of the EGFR family members by androgens in PCa. Hormone response was compared in hormone-sensitive LNCaP and hormone-insensitive DU145 PCa cell lines. These cells do not express ErbB4. EGFR, erbB2 and erbB3 protein half-life is much longer in DU145 than in LNCaP cells grown in complete medium. Dihydrotestosterone (DHT) modulates EGFR and erbB2 transcript and protein levels only in LNCaP cells. ErbB3 is not an androgen-responsive gene. EGFR mRNA and protein levels are increased while erbB2 mRNA and protein levels are decreased after DHT treatment of cells cultured in steroid-deprived medium. ErbB2 mRNA and protein levels are increased in LNCaP cells following DHT withdrawal. In order to understand the mechanisms by which androgens control the expression of EGFR and ERBB2 genes, half lifes of the corresponding mRNAs and proteins were compared in cells grown in presence or absence of DHT. The effect of DHT on EGFR gene expression is complex. Indeed, DHT stabilizes the protein. Moreover, a superinduction of EGFR mRNA was observed in cells treated with cycloheximide (CHX) before addition of the hormone, suggesting an effect on transcript stability. In contrast, erbB2 mRNA and protein stability was not affected by DHT. CHX treatment for 2h before addition of DHT suppresses the androgen-induced down-regulation of erbB2 mRNA levels. In summary, androgen-mediated regulation of EGFR and ERBB2 genes expression is complex. DHT influences EGFR gene transcription, mRNA and protein stability. DHT does not affect erbB2 mRNA and protein stability but acts indirectly on transcription. Current experiments are undertaken to verify these observations by Chromatin-IP experiments on both genes promoters. [less ▲]

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See detailSodium butyrate and trichostatin-a induce apoptosis in human breast cancer cells but not in normal human mammary epithelial cells
Locigno, Roberto; Henno, Audrey ULg; Waltregny, David ULg et al

in Proceedings of the American Association for Cancer Research (2001), 42

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See detailIncreased expression of Galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients
van den Brule, Frédéric; Waltregny, David ULg; Castronovo, Vincenzo ULg

in Proceedings of the American Association for Cancer Research (2000), 41

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See detail(E)-2'-Deoxy-2'-(Fluoromethylene)cytidine potentiates radioresponse of two human solid tumor xenografts.
Sun, L-Q; Li, Y-X; Guillou, L et al

in Proceedings of the American Association for Cancer Research (1998)

Antitumor and radiosensitizing effects of (E)-2'-deoxy-2'-(fluoromethylene) cytidine (FMdC), a novel inhibitor of ribonucleotide reducÃase, were evaluated on nude mice bearing s.c. human C33-A cervix ... [more ▼]

Antitumor and radiosensitizing effects of (E)-2'-deoxy-2'-(fluoromethylene) cytidine (FMdC), a novel inhibitor of ribonucleotide reducÃase, were evaluated on nude mice bearing s.c. human C33-A cervix cancer and I -H7 MG glioblastoma xenografts. FMdC given once daily has a dosedependent antitumor effect. The maximum tolerated dose in the mice was reached with 10 daily i.p. administrations of 10 mg/kg over 12 days. In the case of radiotherapy (RT) alone (10 fractions over 12 days), the radiation dose required to produce local tumor control in 50% of the treated C33-A xenografts was 51.0 Gy. When combined with FMdC, the radiation dose required to produce local tumor control was reduced to 41.4 and 38.2 Gy, at respective doses of 5 and 10 mg/kg given i.p. l h before each irradiation. The corresponding enhancement ratios (ERs) were 1.2 and 1.3, respec tively. In U-87 MG xenografts, when 5-20 mg/kg FMdC combined with 30 or 40 Gy of RT, the combination treatment produced a significantly increased growth delay as compared with RT alone (P £0.002). The ERs of 5, 10, and 20 mg/kg FMdC at a dose of 30 Gy were 2.0, 1.4, and 1.8, respectively. At the 40-Gy level, ERs of 10 and 20 mg/kg FMdC were 1.4 and 1.7. When FMdC was combined with 50 Gy of RT, an increased long-term remission rate of 80-88.9% was observed, as compared with 25% for RT alone (P <0.05). FMdC produced moderate myelosuppression in the mice bearing cervix cancer, whereas leukocytosis occurred in the mice bearing glioblastoma at a low dose. Slightly increased skin toxicity (only with U-87 MG tumor) was observed, as compared with RT alone. In conclusion, FMdC is a potent cytotoxic agent and able to modify the radiation response of C33-A and U-87 MG xenografts. [less ▲]

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See detailExpression of bone sialoprotein in human prostate cancer is associated with progression
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

in Proceedings of the American Association for Cancer Research (1998), 39

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See detailBone sialoprotein is expressed in both human neuroblastoma tissues and cell lines
Bellahcene, Akeila ULg; Albert, Valérie; Nyabi, Omar et al

in Proceedings of the American Association for Cancer Research (1998), 39

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See detailOverexpression of the 67-kD laminin receptor correlates with tumor progression in human prostate cancer
Waltregny, David ULg; de Leval, Laurence ULg; Ménard, Sylvie et al

in Proceedings of the American Association for Cancer Research (1997), 38

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