Although EBV infection is ubiquitous among human population and causes self-limiting infectious mononucleosis in young adolescents, it is strongly associated with several human malignancies such as Burkitt\#8217;s lymphoma (BL), Hodgkin\#8217;s disease (HD), nasopharyngeal carcinoma (NPC), posttransplantation lymphoproliferative disease (PTLD) and some sporadic cancers of breast and gastrointestinal tract. In these diseases EBV maintains a state of latency by restricting expression of about 90% of it genes and thus evades immune surveillance. Only eleven EBV gene products are expressed in these malignancies. The precise role of these latent gene products in EBV pathogenesis is not well understood. However, latent membrane protein 1 (LMP1) and non-coding small RNA (EBERs) have been implicated in the genesis of EBV-associated tumors. A recent study demonstrated that EBV infection of an estrogen receptor negative breast cancer cell line MDA-MB-231 activates expression of multidrug resistant protein MDR1. This observation suggests expansion of the harmful repertoire of EBV in EBV-associated tumors. Because of the significance of MDR phenotype in cancer patients, we initiated investigation on the mechanism of MDR1 expression in EBV infected mammary cell lines. We tested the effect of expression of various latent EBV gene products on MDR1 expression in estrogen receptor positive MCF-7 cells. We generated MCF-7 cell derivatives that stably expressed LMP1, EBERs or another latent gene product, BamH1 A rightward transcript (BART). We analyzed total RNA preparations from these cells by reverse transcription and real time PCR analysis for the expression of MDR1 and MDR related protein (MRP). Our data indicated that expression of non-coding RNA EBER activated MDR1 expression in this cell line. Analysis of the sensitivity of the cells that stably expressed EBER, to chemotherapeutic drug paclitaxel showed that such expression also made the MCF-7 cells resistant to paclitaxel. Our studies warrant that the effect of EBER and other latent EBV gene products are tested on multiple estrogen receptor-positive and -negative breast cancer cell lines as well as for their ability to induce drug resistance in animal models of tumorigenesis. These studies will be highly beneficial to formulate new therapeutic avenues for EBV-associated cancers of the breast and other organs that acquire MDR phenotype.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1868.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009