Madhavan Jagadeesan, Mitra Moutushy, Mallikarjuna Kandalam, Pranav Oberoi, Srinivasan Ramalingam, Nagpal Amit, Venkatesan Perumal, Kumaramanickavel Govindasamy
Sankara Nethralaya Oil and Natural Gas Corporation (SNONGC), Department of Genetics and Molecular Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
Mol Vis. 2009;15:235-40. Epub 2009 Jan 26.
We quantified mRNA expression of candidate genes for proliferation (KIF14 and E2F3) in a large retinoblastoma tumor cohort and associated with disease phenotype.
KIF14 and E2F3 mRNA expression was quantified by real time PCR in 57 retinoblastoma (RB) tumors, 3 RB cell lines, and control samples that included 4 each fetal, age-matched, adult retinas. Immunohistochemistry was done to confirm KIF14 and E2F3 protein expression in tumor cells. The mRNA expression levels were correlated with disease phenotypes including the significance of chemotherapy on tumors.
There was statistically significant overexpression of KIF14 and E2F3 mRNA in tumors compared with control retinas (p<0.0001). Further, E2F3 also showed a significant overexpression compared to RB cell lines (p=0.01). Immunohistochemistry confirmed KIF14 and E2F3 protein overexpression in tumor cells. KIF14 had significant mRNA overexpression with older age (p=0.01) in presenting patients and in unilateral RB patients (p=0.04). Chemotherapy-treated tumors showed a significant decrease in KIF14 and E2F3 expression compared to untreated tumors (p<0.01 and 0.001, respectively).
This report confirms significant mRNA overexpression of KIF14 and E2F3 together in a large cohort of RB tumors. The decreased expression in chemotherapy treated cases needs further validation in a large chemotherapy-treated cohort.
我们在一个大型视网膜母细胞瘤肿瘤队列中对增殖相关候选基因(KIF14和E2F3)的mRNA表达进行了定量,并将其与疾病表型相关联。
通过实时PCR对57例视网膜母细胞瘤(RB)肿瘤、3种RB细胞系以及包括4个胎儿、年龄匹配的成人视网膜的对照样本中的KIF14和E2F3 mRNA表达进行定量。进行免疫组织化学以确认肿瘤细胞中KIF14和E2F3蛋白的表达。mRNA表达水平与疾病表型相关,包括化疗对肿瘤的意义。
与对照视网膜相比,肿瘤中KIF14和E2F3 mRNA有统计学意义的过表达(p<0.0001)。此外,与RB细胞系相比,E2F3也有显著的过表达(p=0.01)。免疫组织化学证实肿瘤细胞中KIF14和E2F3蛋白过表达。在就诊患者和单侧RB患者中,KIF14的mRNA表达随年龄增长有显著过表达(p=0.01和p=0.04)。与未治疗的肿瘤相比,化疗治疗的肿瘤中KIF14和E2F3表达显著降低(分别为p<0.01和0.001)。
本报告证实在一大群RB肿瘤中KIF14和E2F3共同有显著的mRNA过表达。化疗治疗病例中表达的降低需要在一个大型化疗治疗队列中进一步验证。