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Expression of MDR1, HIF-1α and MRP1 in sacral chordoma and chordoma cell line CM-319 - PubMed

️Fri Jan 01 2010

Expression of MDR1, HIF-1α and MRP1 in sacral chordoma and chordoma cell line CM-319

Zhengang Ji et al. J Exp Clin Cancer Res. 2010.

Abstract

Background: Chordoma was a typically slow-growing tumor. The therapeutic approach to chordoma had traditionally relied mainly on surgical therapy. And the main reason for therapeutic failure was resistance to chemotherapy and radiotherapy. However the refractory mechanism was not clear. The aim of this study was to investigate the expression of three genes (MDR1, HIF-1α and MRP1) associated with resistance to chemotherapy and radiotherapy in chordoma and chordoma cell line CM-319.

Materials and methods: Using immunohistochemical techniques, the expression of MDR1, HIF-1α and MRP1 was investigated in 50 chordoma specimen. Using RT-PCR and Western blot, the expression of MDR1, HIF-1α and MRP1 was investigated in chordoma and chordoma cell line CM-319.

Results: Expression of MDR1, HIF-1α and MRP1 was observed in 10%, 80% and 74% of all cases, respectively. Expression of MRP1 was correlated with HIF-1α. On the other hand, expression of MDR1 was not correlated with the expression of HIF-1α or MRP1. The expression of HIF-1α and MRP1 was observed, but MDR1 was not observed in chordoma and CM-319.

Conclusion: Expression of HIF-1α and MRP1 was observed in most chordoma specimen and CM-319 cell line; expression of HIF-1α correlated with MRP1. HIF-1α and MRP1 may play a role in the multidrug resistance of chordoma to chemotherapy.

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Figures

**Figure 1**
**Immunohistochemical staining of HIF-1α, MDR1 and MRP1 in chordoma, CM-319 and nucleus pulpous**. With immunohistochemical staining, the expression of chemotherapy resistant proteins using primary antibody to HIF-1α (A, B, G), MDR1 (E, F, I) and MRP1 (C, D, H) was determined in chordoma (B, D, F) and CM-319 (A, C, E). Intense membrane and cytoplasmic staining of MRP1 (×400) and cytoplasmic and nuclus staining of HIF (×400). Negative immunostaining of MDR1 was found in chordoma and CM-319. In control, negative immunostaining of HIF-1, MRP1 and MDR1 (G, H, I) was found in nucleus pulposus.

**Figure 2**
**RT-PCR analysis of *MDR1*, *HIF-1α* and *MRP1* messenger RNA (mRNA) expression in CM-319 cell line and chordoma**. A significant *HIF-1α* and *MRP1* mRNA expression was observed, but a negative *MDR1* expression was observed in CM-319 cell line and chordomas. But negative expression of *MDR1*, *HIF-1α* and *MRP1* messenger RNA (mRNA) in nucleus pulposus. Amplification of a 547-bp fragment of *GAPDH* was used as an internal control for the integrity of the isolated mRNA. Lane 1: Marker; Lane 2: GAPDH; Lane 3: HIF-1α; Lane 4: MRP1; Lane 5: MDR1.

**Figure 3**
**Western blot analysis of HIF-1α, MDR1 and MRP1 protein in tumor tissues and CM-319 cell line**. Lane1: MRP1; lane2: HIF-1α; lane 3: MDR1; lane4: conditioned medium. Molecular weight markers are identificated in the left side (kD).

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Expression of MDR1, HIF-1α and MRP1 in sacral chordoma and chordoma cell line CM-319 - PubMed