Yang D C, Wang F, Elliott R L, Head J F
Mastology Research Institute, Elliott Mastology Center, Baton Rouge, LA 70806, USA.
Anticancer Res. 2001 Jan-Feb;21(1B):541-9.
It is well known that iron plays an essential role in many biochemical reactions and that rapidly growing cells require more iron for their growth and metabolism than resting cells. Transferrin and its receptor are required for entry of iron into the cell. In contrast, ferritin is a cellular storage protein whose main function is to sequester excess ferric iron and thus prevent high concentrations of soluble ferric iron from becoming toxic to the cell. However, the clinical significance of both transferrin receptor and ferritin mRNA levels have not previously been described in tumors from breast cancer patients. In this study, tumor tissue mRNA levels of transferrin receptor and ferritin were quantitated on forty-two breast cancer patients. A highly sensitive non-radioisotopic cDNA polymerase chain reaction assay was used to quantitate expression of mRNA. The expression of glyceraldehyde-3-phosphate dehydrogenase served as the control. In the tumor tissue from the 42 breast cancer patients the transferrin receptor mRNA levels were significantly correlated to the ferritin H-chain mRNA levels (Spearman correlation r = 0.5433, p = 0.0002; Pearson correlation r = 0.6276, p < 0.0001). The level of amplified transferrin receptor complementary DNA was related to differentiation (ANOVA, p = 0.042) with poorly differentiated tumors having high levels of transferrin receptor mRNA. Further, the levels of amplified gene for ferritin heavy chain complementary DNA was directly related to axillary lymph nodes status (Student's t-test, p = 0.044), presence of metastatic disease (Student's t-test, p = 0.046) and clinical stage (stage I + stage II versus stage III + stage IV; Student's t-test, p = 0.0181). These results demonstrate that non-radioisotopic RT-PCR is a very sensitive method for determining mRNA levels in tumor tissue. Additionally, the quantitation of expression of transferrin receptor and ferritin heavy chain mRNA may be useful for assessing prognosis and guiding therapeutic decisions in breast cancer patients.
众所周知，铁在许多生化反应中起着至关重要的作用，并且快速生长的细胞在其生长和代谢过程中比静止细胞需要更多的铁。转铁蛋白及其受体是铁进入细胞所必需的。相比之下，铁蛋白是一种细胞储存蛋白，其主要功能是螯合过量的三价铁，从而防止高浓度的可溶性三价铁对细胞产生毒性。然而，转铁蛋白受体和铁蛋白mRNA水平在乳腺癌患者肿瘤中的临床意义此前尚未见报道。在本研究中，对42例乳腺癌患者的肿瘤组织中转铁蛋白受体和铁蛋白的mRNA水平进行了定量分析。采用一种高度灵敏的非放射性cDNA聚合酶链反应分析法对mRNA表达进行定量。以甘油醛-3-磷酸脱氢酶的表达作为对照。在42例乳腺癌患者的肿瘤组织中，转铁蛋白受体mRNA水平与铁蛋白H链mRNA水平显著相关（Spearman相关系数r = 0.5433，p = 0.0002；Pearson相关系数r = 0.6276，p < 0.0001）。扩增的转铁蛋白受体互补DNA水平与分化程度相关（方差分析，p = 0.042），低分化肿瘤的转铁蛋白受体mRNA水平较高。此外，铁蛋白重链互补DNA扩增基因的水平与腋窝淋巴结状态（学生t检验，p = 0.044）、转移疾病的存在（学生t检验，p = 0.046）和临床分期（I期+II期与III期+IV期；学生t检验，p = 0.0181）直接相关。这些结果表明，非放射性逆转录聚合酶链反应是一种测定肿瘤组织中mRNA水平的非常灵敏的方法。此外，转铁蛋白受体和铁蛋白重链mRNA表达的定量分析可能有助于评估乳腺癌患者的预后并指导治疗决策。
