Debes Jose D, Sebo Thomas J, Lohse Christine M, Murphy Linda M, Haugen De Anna L, Tindall Donald J
Departments of Urology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Cancer Res. 2003 Nov 15;63(22):7638-40.
Although prostate cancer (PCa) is the most frequently diagnosed cancer in males, little is known about the mechanisms involved in its progression. Recent in vitro studies suggest that coactivators of the androgen receptor play an important role in PCa progression. We have shown previously that p300 is involved in androgen receptor transactivation. In the present work, we studied 95 patients with biopsy-proven PCa who underwent prostatectomy as treatment of their tumors between 1995 and 1998. We found that p300 correlated with in vivo proliferation (P = 0.009) as determined by MIB-I expression. Moreover, high levels of p300 in biopsies predicted larger tumor volumes (P < 0.001), extraprostatic extension (P = 0.003), and seminal vesicle involvement (P = 0.002) at prostatectomy, as well as PCa progression after surgery (P = 0.01). Furthermore, we found that the disruption of p300 transcripts through small interfering RNA inhibited PCa cell proliferation both at the basal level and on interleukin 6 stimulation. We conclude that p300 plays an important role in PCa cell proliferation, as well as PCa progression.
尽管前列腺癌（PCa）是男性中最常被诊断出的癌症，但对其进展所涉及的机制却知之甚少。最近的体外研究表明，雄激素受体的共激活因子在PCa进展中起重要作用。我们之前已经表明p300参与雄激素受体的反式激活。在本研究中，我们对95例经活检证实为PCa的患者进行了研究，这些患者在1995年至1998年间接受了前列腺切除术以治疗他们的肿瘤。我们发现，通过MIB-1表达确定，p300与体内增殖相关（P = 0.009）。此外，活检中p300水平高预示着前列腺切除术中肿瘤体积更大（P < 0.001）、前列腺外扩展（P = 0.003）和精囊受累（P = 0.002），以及术后PCa进展（P = 0.01）。此外，我们发现通过小干扰RNA破坏p300转录本可在基础水平和白细胞介素6刺激下均抑制PCa细胞增殖。我们得出结论，p300在PCa细胞增殖以及PCa进展中起重要作用。
