Garreau Jennifer R, Muller Patrick, Pommier Rodney, Pommier Suellen
Division of Surgical Oncology, Department of Surgery, Oregon Health and Sciences University, 3181 S. W. Sam Jackson Park Rd., L223A, Portland, OR 97201, USA.
Am J Surg. 2006 May;191(5):576-80. doi: 10.1016/j.amjsurg.2006.02.004.
Estrogen-receptor (ER)-, progesterone-receptor (PR)-, and androgen-receptor (AR)-negative breast cancer cells are unaffected by treatment with dehydroepiandrosterone-sulfate (DHEAS) and an aromatase inhibitor (AI). We hypothesized that cell growth would be inhibited with DHEAS/AI treatment after successful transfection of an AR expression vector.
ER/PR/AR-negative breast cancer cells were transfected with an AR expression vector and treated with DHEAS/AI for 2 days. Growth inhibition of these cells was compared with that of transfected cells treated with only AI or with nontransfected cells treated with DHEAS/AI. Mann-Whitney U test was used to determine statistical significance.
Cell death rates of 53.5% (P = .001) and 40.1% (P = .006) were seen in transfected cells treated with DHEAS/AI compared with controls for days 1 and 2, respectively. Nontransfected cells were unaffected by treatment.
ER/PR/AR-negative cells transfected with AR were killed by DHEAS/AI treatment, providing evidence that AR is responsible for this effect. This provides the first AR-targeted hormonal therapy for ER breast cancer.
雌激素受体(ER)、孕激素受体(PR)和雄激素受体(AR)阴性的乳腺癌细胞对硫酸脱氢表雄酮(DHEAS)和芳香化酶抑制剂(AI)治疗无反应。我们假设成功转染AR表达载体后,DHEAS/AI治疗会抑制细胞生长。
用AR表达载体转染ER/PR/AR阴性乳腺癌细胞,并用DHEAS/AI处理2天。将这些细胞的生长抑制情况与仅用AI处理的转染细胞或用DHEAS/AI处理的未转染细胞进行比较。采用曼-惠特尼U检验确定统计学意义。
与对照组相比,用DHEAS/AI处理的转染细胞在第1天和第2天的细胞死亡率分别为53.5%(P = .001)和40.1%(P = .006)。未转染细胞不受该处理影响。
用AR转染的ER/PR/AR阴性细胞经DHEAS/AI处理后死亡,这证明AR是造成这种效应的原因。这为ER乳腺癌提供了首个以AR为靶点的激素疗法。