H-Ras oncogene counteracts the growth-inhibitory effect of genistein in T24 bladder carcinoma cells.

Among eight human bladder cancer cell lines we examined, only T24 cells were resistant to the growth inhibition effect of genistein, an isoflavone and potent anticancer drug. Since the T24 cell line was the only cell line known to overexpress oncogenic H-Ras(val 12), we investigated the role of H-Ras(val 12) in mediating drug resistance. Herein, we demonstrate that the phenotype of T24 cells could be dramatically reversed and became relatively susceptible to growth inhibition by genistein if the synthesis of H-Ras(val 12) or its downstream effector c-Fos had been suppressed. The inhibition of Ras-mediated signalling with protein kinase inhibitors, such as PD58059 and U0126 which inhibited MEK and ERK, in T24 cells also rendered the identical phenotypic reversion. However, this reversion was not observed when an inhibitor was used to suppress the protein phosphorylation function of PI3 K or PKC. These results suggest that the signal mediated by H-Ras(val 12) is predominantly responsible for the resistance of the cells to the anticancer drug genistein.

Unsuspected Prostate Carcinoma and Prostatic Intraepithelial Neoplasm in Taiwanese Patients Undergoing Cystoprostatectomy.

Although the incidence and death rates for cancer of the prostate (CaP) in Taiwan have been among the lowest in the world, they have increased remarkably in recent years. Because of the very low autopsy rate in this country, prostate specimens obtained via cystoprostatectomy may provide a unique opportunity to study the incidence and status of latent cancer. From January 1992 to December 1997, 49 prostate specimens were obtained from patients with transitional-cell carcinoma of the urinary bladder (48 cases) or pelvic melanoma (one case). Patients' ages ranged from 47 to 89, with a mean age of 67.8 years. No patient had any clinical indication of CaP, as assessed by digital rectal examination. Each prostate was prepared with whole-mount transverse serial sections at 3-mm intervals from the apex to the bladder neck. The stained slides reviewed by two pathologists to evaluate the frequency and pathological status of acinar cancer lesions and high-grade prostatic intraepithelial neoplasia (PIN). Of the 49 patients evaluated, 16 (33%) had evidence of adenocarcinoma, and 24 (49%) had high-grade PIN. The incidence of unsuspected CaP in patients aged 40 to 59, 60 to 69, and >/=70 years was 25%, 32%, and 37%, respectively. The frequency of high-grade PIN in patients aged 40 to 59, 60 to 69, and >/=70 years was 25%, 42%, and 64%, respectively. The incidence of high-grade PIN in the 16 patients with unsuspected CaP was significantly higher than in the 31 patients without this early cancer (75% v 36%). Of the 16 patients with unsuspected cancer, 5 had multiple tumors (3 patients with two and 2 with multiple foci). The mean volume of the 24 tumors was 0.0786 cm(3), with a range of 0.008 to 0.393 cm(3), but only 6 tumors exceeded 0.1 cm(3) in volume (0.112, 0.112, 0.164, 0.245, 0.262, and 0.393 cm(3)). Eighty-eight percent of these early cancers were low grade (Gleason score 2-4). All unsuspected CaP were organ confined. The frequency of unsuspected CaP in Taiwanese men is relatively higher than in Chinese, as previous reported by Dr. Gu. However, the incidence of this latent cancer is comparable to that of U.S. men of the same age. These findings, together with the high incidence of high-grade PIN, suggest that the initial step in the induction of CaP in indigenous Taiwanese is similar to that in U.S. men. The lower number of reports of CaP in Taiwan might be attributable to: (1) lower volume of latent cancer in the Taiwanese compared with U.S. men; (2) underestimation of the incidence rate of CaP in Taiwan; or (3) different genetic or environmental status leading to a different progression rate.