ABSTRACT.One of the limitations in the treatment of cancer patients with chemotherapy is the development of multidrug resistance (MDR). A well-known mechanism responsible for drug resistance is over-expression of ABC-transporter genes such as MDR1. This gene encodes p-glycoprotein (P-gp), a transmembrane glycoprotein that transports many hydrophobic substrates and anti-cancer drugs out of the cell. MDR1 gene polymorphisms could alter the expression level of P-gp and consequently result in drug resistance. We investigated a possible association between MDR1 gene C3435T polymorphism and its expression in Iranian breast cancer patients. PCR-RFLP was used for the detection of C3435T single nucleotide polymorphism in 54 breast cancer patients and 50 healthy individuals. The expression level of MDR1 was determined by real-time quantitative PCR. We observed no difference in the frequency of C3435T polymorphism between breast cancer patients and healthy controls. However, 35©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 9 (1): 34-40 (2010) MDR1 polymorphism in breast cancer patients there was a significant association between MDR1 expression levels and C3435T polymorphism in the patients. C3435T polymorphism may play a role in inducing drug resistance by altering the expression level of the MDR1 gene.

Abstract. A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR) assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor.

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CONTEXT AND OBJECTIVE: Overexpression of the multidrug resistance-associated protein 1 (MRP1) gene has been linked with resistance to chemotherapy in vitro, but little is known about its clinical impact on acute leukemia patients. Our aim was to investigate the possible association between MRP1 gene expression level and clinical outcomes among Iranian leukemia patients. DESIGN AND SETTING:This was an analytical cross-sectional study on patients referred to the Hematology, Oncology and Stem Cell Research Center, Sharyatee Public Hospital, whose diagnosis was acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL). All molecular work was performed at NIGEB (public institution). METHODS:To correlate with prognostic markers and the clinical outcome of acute leukemia, MRP1 gene expression was assessed in 35 AML cases and 17 ALL cases, using the quantitative real-time polymerase chain reaction and comparing this to the chemotherapy response type. RESULTS:Mean expression in AML patients in complete remission (0.032 ± 0.031) was significantly lower than in relapsed cases (0.422 ± 0.297). In contrast, no signifi cant difference in MRP1 mRNA level was observed between complete remission and relapsed ALL patients. There was a difference in MRP1 expression between patients with unfavorable and favorable cytogenetic prognosis (0.670 ± 0.074 and 0.028 ± 0.013, respectively). MRP1 expression in M5 was signifi cantly higher (p-value = 0.001) than in other subtypes. CONCLUSIONS:The fi ndings suggest that high MRP1 expression was associated with poor clinical outcome and was correlated with the M5 subtype and poor cytogenetic subgroups among AML patients but not among ALL patients.

BACKGROUND Colorectal cancer (CRC) is one of the most common cancers among men and women worldwide. Cancer metastasis is the main cause of death in patients with cancer. NEBL (nebulette, Gene ID: 10529) protein interacts with thin filaments in the cell and may functionally destabilize focal adhesion composition. There are some studies on NEBL gene expression alteration in cancer. In the presented study we aimed to analyze NEBL gene expression in patients with colorectal cancer to explore possible association of this gene with clinicopathological features in CRC. METHODS Sixty-seven fresh samples of colorectal tumors and adjacent normal tissues were collected from Iranian patients with CRC. Real time polymerase chain reaction was performed to measure the level of NEBL gene expression and its association with clinico-pathological features. RESULTS A significant overexpression with 3 fold increse was seen in NEBL mRNA level in tumoral tissues compared with the adjacent normal tissues. In addition there was a significant association between NEBL gene expression with lymph node metastasis in patients with CRC. CONCLUSION The overexpression of NEBL has the capacity to be considred as a prognostic biomarker in patients with CRC.