Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo: implications for lung cancer development.
Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo: implications for lung cancer development.
复制标题
体内非小细胞肺癌中视黄酸受体β的抑制：对肺癌发展的影响。
DOI：
10.1093/jnci/89.9.624
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Lotan,R
中科院分区：
文献类型：
--
作者：
Xu,XC;Sozzi,G;Lee,JS;Lee,JJ;Pastorino,U;Pilotti,S;Kurie,JM;Hong,WK;Lotan,R
背景：类维生素A是维生素A的类似物，是人类支气管上皮正常生长和分化所必需的。它们还能够逆转某些非小细胞肺癌（NSCLC）患者的癌前病变并预防第二原发肿瘤。这些效应被认为是细胞生长、分化或细胞凋亡（程序性细胞死亡）调节的结果。当细胞核中介导大多数类维生素A作用的某些类维生素A受体（即类维生素A酸受体[RAR]和类维生素AX受体[RXR]）受到抑制时，可能会导致异常活性，从而促进癌症的发展。目的：本研究旨在确定 NSCLC 患者手术标本中视黄醇受体的表达是否存在异常。方法：使用地高辛标记的 RARα、RARβ、RARγ、RXRα、RXRβ 和 RXRγ 特异核糖核酸探针，与 79 例 NSCLC 患者的组织学样本和 17 例非肺癌患者的对照样本进行原位杂交，检测福尔马林固定、石蜡包埋的样本中核视黄酸受体的转录本。通过Northern印迹测定地高辛标记探针的质量和特异性，并通过使用正义探针作为对照来验证反义核糖核酸探针结合的特异性。结果：所有受体在 17 名非原发性肺癌患者的对照正常支气管组织标本和 NSCLC 患者的远处正常支气管标本中至少 89% 表达。 RARα、RXRα 和 RXRγ 在超过 95% 的 NSCLC 样本中表达。相比之下，RARβ、RARγ 和 RXRβ 表达分别仅在 42%、72% 和 76% 的 NSCLC 中检测到。结论：这些数据表明，RARα、RXRα 和 RXRγ 的表达在 NSCLC 中没有改变；然而，RAR 的表达以及 RAR 和 RXR 的表达在大部分肺癌患者中均受到抑制。意义：一种或多种核类视黄醇受体表达的丧失可能与肺癌发生有关。[J Natl Cancer Inst 1997；J Natl Cancer Inst 1997] 89: 624-9]肺癌仍然是癌症死亡的主要原因。这种癌症在男性和女性中的发病率都在持续增加，女性肺癌死亡率已超过乳腺癌。据估计，1997年美国将有178 100个新病例和160 400人死于肺癌(1)。尽管治疗取得了进步，但肺癌患者的总体 5 年生存率仍低于 13%。因此，迫切需要确定和使用预防和治疗肺癌的新方法。其中一种方法是使用类维生素A（维生素 A 的结构和功能类似物）进行化学预防 (2)。类视黄醇适合这种策略，因为它们调节气道上皮的分化 (3) 并抑制多种肺癌动物模型的癌变 (4, 5)。有趣的是，维生素 A 缺乏与肺癌发病率增加有关 (6)。此外，某些类视黄醇可抑制口腔癌前病变，并预防头颈癌和肺癌患者第二原发癌的发展 (7, 8)。
Background: Retinoids, analogues of vitamin A, are required for the normal growth and differentiation of human bronchial epithelium. They are also able to reverse premalignant lesions and prevent second primary tumors in some patients with non-small-cell lung cancer (NSCLC). These effects are thought to result from modulation of cell growth, differentiation, or apoptosis (programmed cell death). When certain retinoid receptors in the cell nucleus (ie, retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which mediate most retinoid actions, are suppressed, abnormal activity may result that could enhance cancer development. Purpose: This study was designed to determine whether there are abnormalities in the expression of retinoid receptors in surgical specimens from patients with NSCLC. Methods: Transcripts of nuclear retinoid receptors were detected in formalin-fixed, paraffin-embedded specimens by use of digoxigenin-labeled riboprobes specific for RARα, RARβ, RARγ, RXRα, RXRβ, and RXRγ for in situ hybridization to histologic specimens from 79 patients with NSCLC and as control from 17 patients with non-lung cancer. The quality and specificity of the digoxigenin-labeled probes were determined by northern blotting, and the specificity of the binding of antisense riboprobes was verified by use of sense probes as controls. Results: All receptors were expressed in at least 89% of control normal bronchial tissue specimens from 17 patients without a primary lung cancer and in distant normal bronchus specimens from patients with NSCLC. RARα, RXRα, and RXRγ were expressed in more than 95% of the NSCLC specimens. In contrast, RARβ, RARγ, and RXRβ EXPRESSION WAS DETECTED IN ONLY 42%, 72%, and 76% of NSCLC, respectively. Conclusions: These data suggest that the expression of RARα, RXRα, and RXRγ is not altered in NSCLC; however, expression of RAR and possibly also of RAR and RXR is suppressed in a large percentage of patients with lung cancer. Implications: The loss of expression of one or more of these nuclear retinoid receptors may be associated with lung carcinogenesis.[J Natl Cancer Inst 1997; 89: 624-9]Lung cancer is still the leading cause of cancer death. The incidence of this cancer continues to increase in both men and women, and mortality from lung cancer has surpassed that from breast cancer in women. It has been estimated that there will be 178 100 new cases and 160 400 deaths from lung cancers in the United States in 1997 (1). Despite advances in therapy, the overall 5-year survival rate of patients with lung cancer is still under 13%. Therefore, the identification and use of novel approaches for the prevention and treatment of lung cancer are urgently needed. One such approach is to use retinoids, structural and functional analogues of vitamin A, for chemoprevention (2). Retinoids are suitable for this strategy because they regulate differentiation in airway epithelium (3) and suppress carcinogenesis in a variety of animal models for lung cancer (4, 5). Interestingly, vitamin A deficiency has been associated with increased lung cancer incidence (6). Furthermore, certain retinoids suppress premalignant oral lesions and prevent the development of second primary cancers among patients with head and neck and lung cancer (7, 8).
登录
查看更多内容
类维生素A化学预防呼吸消化道癌症：从基础研究到临床。
DOI：
--
发表时间：
1995
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research.
影响因子：
--
作者：
KiHong,W;Lippman,SM;Hittelman,WN;Lotan,R
通讯作者：
Lotan,R
视黄酸受体γ在头颈SqCC/Y1鳞状癌细胞鳞状细胞分化和对视黄酸反应中的意义。
DOI：
--
发表时间：
1996
期刊：
Oncogene.
影响因子：
--
作者：
Oridate,N;Esumi,N;Lotan,D;Hing,WK;Rochette-Egly,C;Chambon,P;Lotan,R
通讯作者：
Lotan,R
人类肺癌中视黄酸受体β异常的发生率较高。
影响因子：
8
作者：
Gebert,JF;Moghal,N;Frangioni,JV;Sugarbaker,DJ;Neel,BG
通讯作者：
Neel,BG
肺癌和上呼吸消化道癌症化学预防剂的开发
DOI：
--
发表时间：
1993
期刊：
Journal of cellular biochemistry. Supplement
影响因子：
--
作者：
G. Kelloff;C. Boone;Vernon K. Steele;M. Perloff;J. Crowell;L. Doody
通讯作者：
L. Doody
影响因子：
11.2
作者：
X. C. Xu;Jae Y. Ro;J. S. Lee;Dong M. Shin;W. Hong;R. Lotan
通讯作者：
X. C. Xu;Jae Y. Ro;J. S. Lee;Dong M. Shin;W. Hong;R. Lotan