Increased LZTS1 expression is associated with a good response to paclitaxel-based chemotherapy in breast cancer

Abstract

Leucine zipper putative tumor suppressor 1 (LZTS1) is a tumor suppressor gene located on chromosome 8p22, and the expression is usually decreased in different types of cancers. Here we analyze the correlation between LZTS1 and paclitaxel sensitivity to breast cancer. LZTS1 expression was investigated in MDA-MB-231 cell line by reverse transcriptase-polymerase chain reaction(RT-PCR) and western blot. Cell cycle and apoptosis were detected using flow cytometry. Cell proliferation/viability assays to test drug sensitivity in breast cancer cell line. Human tumor xenograft models to measure chemo-sensitivity in LZTS1 over-expression tumor. The expression of LZTS1 was detected using immunohistochemistry in breast cancer, and the correlation between the LZTS1expression and the effect of chemotherapy was analyzed. In vitro cell proliferation assays revealed that LZTS1 expression was correlated with paclitaxel sensitivity in breast cancer cells. Cell cycle analysis and apoptosis experiments have demonstrated that LZTS1 could enhance the inhibitory effect of paclitaxel on the breast cancer cell cycle and the ability to induce apoptosis. Overexpression of LZTS1 could sensitize human breast carcinoma xenografts to paclitaxel. In addition, tumor with high LZTS1 expression was more sensitive to chemotherapy with paclitaxel in breast cancer. For the first time, we evaluated the relationship between LZTS1 expression and chemotherapy sensitivity using the Collagen gel droplet drug sensitivity test(CD-DST) in primary cell culture of breast cancer. LZTS1 may play an important role in improving the sensitivity of paclitaxel-based breast cancer chemotherapy.