The role of protein kinase C alpha in recurrence of superficial bladder carcinoma / 中华外科杂志
Chinese Journal of Surgery
;
(12): 662-666, 2005.
Artículo
en Chino
| WPRIM
| ID: wpr-264446
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship of protein kinase C-alpha (PKCalpha) expression/activation with tumor differentiation and resistance to chemotherapy drugs in superficial bladder carcinoma.</p><p><b>METHODS</b>Expression of PKCalpha was measured by Western-blot analysis in 76 samples including tumor and normal tissues, respectively. A human RT4 bladder cancer cell line stably expressing green fluorescent protein (GFP)-PKCalpha (RT4/PKCalpha) was established. The sensitivity of the RT4/PKCalpha and parental cells to adriamycin (ADM) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The change of sensitivity of the RT4/PKCalpha to ADM were observed under the conditions of PKC activation and inhibition, respectively.</p><p><b>RESULTS</b>Total level of PKCalpha expression and the ratio of the amount of PKCalpha expression or PKC activity in membrane to that in cytosol (M/C) were all more higher in cancerous tissues than in normal tissues (P < 0.01); With the increase of tumor grade, the relative level of PKCalpha expression significantly increased in membrane (P < 0.01) and decreased in cytosol (P < 0.01), M/C of PKCalpha was significantly elevated (P < 0.01), and total relative level of PKCalpha expression significantly increased (P < 0.01). Thirty-eight cases recurred during the follow-up period in total seventy cases. Multivariate analysis showed that high M/C of PKCalpha was independent prognostic factor for tumor recurrence after standard ADM treatment in the 2-year follow-up (RR = 3.98, 95% CI 1.22-5.68, P = 0.03). Transfection of PKCalpha increased resistance of RT4 cells to ADM [resistance index (RI) 6.97, t = 3.24, P < 0.01]. PKCalpha activation further greatly promoted the resistance (RI 148.11, t = 5.18, P < 0.001) while inhibition of PKCalpha did conversely (RI 1.6, t = 1.29, P > 0.05).</p><p><b>CONCLUSION</b>The abnormal activation and expression level of PKCalpha closely correlate with both tumor grade and intrinsic resistance to ADM in patients with superficial bladder carcinoma.</p>
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Patología
/
Farmacología
/
Fisiología
/
Neoplasias de la Vejiga Urinaria
/
Células Tumorales Cultivadas
/
Carcinoma de Células Transicionales
/
Transfección
/
Doxorrubicina
/
Estudios de Seguimiento
/
Resistencia a Antineoplásicos
Tipo de estudio:
Estudio observacional
/
Estudio pronóstico
Límite:
Anciano
/
Femenino
/
Humanos
/
Masculino
Idioma:
Chino
Revista:
Chinese Journal of Surgery
Año:
2005
Tipo del documento:
Artículo
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