Goldstein L J, Galski H, Fojo A, Willingham M, Lai S L, Gazdar A, Pirker R, Green A, Crist W, Brodeur G M
Division of Cancer Biology and Diagnosis, National Cancer Institute, Bethesda, MD 20892.
J Natl Cancer Inst. 1989 Jan 18;81(2):116-24. doi: 10.1093/jnci/81.2.116.
Many cancers have been cured by chemotherapeutic agents. However, other cancers are intrinsically drug resistant, and some acquire resistance following chemotherapy. Cloning of the cDNA for the human MDR1 gene (also known as PGY1), which encodes the multidrug efflux protein P-glycoprotein, has made it possible to measure levels of MDR1 RNA in human cancers. We report the levels of MDR1 RNA in greater than 400 human cancers. MDR1 RNA levels were usually elevated in untreated, intrinsically drug-resistant tumors, including those derived from the colon, kidney, adrenal gland, liver, and pancreas, as well as in carcinoid tumors, chronic myelogenous leukemia in blast crisis, and cell lines of non-small cell carcinoma of the lung (NSCLC) with neuroendocrine properties. MDR1 RNA levels were occasionally elevated in other untreated cancers, including neuroblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma. MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma. Many types of drug-sensitive and drug-resistant tumors, including NSCLC and melanoma, contained undetectable or low levels of MDR1 RNA. The consistent association of MDR1 expression with several intrinsically resistant cancers and the increased expression of the MDR1 gene in certain cancers with acquired drug resistance indicate that the MDR1 gene contributes to multidrug resistance in many human cancers. Thus, evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents. The information may be useful in designing or altering chemotherapeutic protocols in these patients.
许多癌症已通过化疗药物治愈。然而，其他癌症具有内在的耐药性，并且一些癌症在化疗后会产生耐药性。人类MDR1基因（也称为PGY1）的cDNA克隆，该基因编码多药外排蛋白P-糖蛋白，使得测量人类癌症中MDR1 RNA的水平成为可能。我们报告了400多种人类癌症中MDR1 RNA的水平。MDR1 RNA水平通常在未经治疗的、具有内在耐药性的肿瘤中升高，包括那些源自结肠、肾脏、肾上腺、肝脏和胰腺的肿瘤，以及类癌、急变期慢性粒细胞白血病和具有神经内分泌特性的非小细胞肺癌（NSCLC）细胞系。MDR1 RNA水平偶尔在其他未经治疗的癌症中升高，包括神经母细胞瘤、成人急性淋巴细胞白血病（ALL）、成人急性非淋巴细胞白血病（ANLL）和惰性非霍奇金淋巴瘤。MDR1 RNA水平在某些化疗后复发的癌症中也会升高，包括ALL、ANLL、乳腺癌、神经母细胞瘤、嗜铬细胞瘤和结节性、低分化淋巴瘤。许多类型的敏感和耐药肿瘤，包括NSCLC和黑色素瘤，含有无法检测到或低水平的MDR1 RNA。MDR1表达与几种内在耐药癌症的一致关联以及MDR1基因在某些获得性耐药癌症中的表达增加表明，MDR1基因在许多人类癌症中导致多药耐药。因此，评估MDR1基因表达可能被证明是识别其癌症对特定药物耐药的个体的有价值工具。这些信息可能有助于设计或改变这些患者的化疗方案。
