Correlation of NIS mRNA levels with radioiodide uptake in mammary tumors and non-tumor mammary glands of MMTV-infected mice

Abstract

We have developed an in vivo non-invasive gamma camera imaging system which uses 125I to detect functional iodide metabolism in mammary tumors. Iodide metabolism in these tumors is mediated by the sodium iodide symporter. The quantity and pattern of radioiodide uptake varies between mammary tumors. We have previously shown that localization of NIS protein expression reflects the radioiodide uptake in gamma camera images. In this study, we investigate whether expression levels of NIS mRNA in mammary tumors correlate with 125I uptake pattern shown in gamma camera images. Our hypothesis is that NIS function in mammary tumors and non-tumor mammary glands is regulated primarily at the transcriptional level. To test this hypothesis, we quantified NIS mRNA levels using TaqMan real-time RT-PCR, and constructed a cRNA standard curve for quantification. The ratio of NIS to the housekeeping gene ?-actin was compared to the intensity and pattern of mammary tumor radioiodide uptake as imaged by the gamma camera. In MMTV tumors, our results suggest that NIS is under both transcriptional and post-transcriptional control in this model for breast cancer. In separate tumors, we observed both positive correlation and no correlation between NIS mRNA level and radioiodide uptake. We also found that NIS mRNA levels were increased in non-palpable tumors in correlation with increases in radioiodide uptake, suggesting that an upregulation of NIS mRNA occurs in early tumor development