Biomedical subjects

M-T Ling

Publications and source records attributed to M-T Ling.

4 recordsLinked to original sources

PubMed2006

Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells.

Testicular germ cell tumour (TGCT) is the most common malignancy in young males. Although most TGCTs are sensitive to cisplatin-based chemotherapy, significant numbers of TGCT patients still relapse and die each year because of the development of resistance to cisplatin. Previously, we first reported that a key regulator of the mitotic checkpoint, mitotic arrest deficient-2 (MAD2), was a mediator of cisplatin sensitivity in human cancer cells. In this study, we investigated whether MAD2 played a role in cellular sensitivity to cisplatin in TGCT cells and the underlying molecular mechanisms responsible. Using 10 TGCT cell lines, we found that increased MAD2 expression was correlated with cellular sensitivity to cisplatin, which was associated with activation of the MEK pathway. Treatment of cells expressing high levels of MAD2 with an MEK inhibitor, U0126, led to cellular protection against cisplatin-induced apoptosis. Inactivation of MAD2 by transfecting a dominant-negative construct in TGCT cells with high levels of MAD2 resulted in the suppression of MEK pathway and resistance to cisplatin-induced cell death. These results support previous suggestion on the involvement of mitotic checkpoint in DNA damage response in human cancer cells and demonstrate a possible molecular mechanism responsible for the MAD2-mediated sensitivity to cisplatin in TGCT cells. Our results also suggest that downregulation of MAD2 may be an indicator for identification of TGCT cancer cells that are potentially resistant to cisplatin-based therapy.

Butadienes↗

PubMed2006

Evidence of a novel biomarker, alphas1-Casein, a milk protein, in benign prostate hyperplasia.

Benign prostate hyperplasia (BPH) is a common disease in elderly men. Although it is a non-malignant disease, it has a significant detrimental impact on the quality of life in patients with late-stage disease. Owing to the lack of specific markers, diagnosis of early-stage BPH has been proven unsuccessful. Recently, using two-dimensional electrophoresis, we identified a group of prostatic secretory proteins that are specifically produced by BPH cells (Xu et al., Electrophoresis 2003; 24: 1311). In this study, we investigated the potential diagnostic value of one of the secretory proteins, alphas1-Casein, in BPH by inmmunohistological staining of normal, BPH and prostate cancer tissues. We found that 90% (20 out of 22) of BPH tissues showed moderate to strong alphas1-Casein protein expression whereas none of the normal tissues (0 out of 10) and less than 10% of the prostate cancer tissues (3 out of 30) showed similar staining intensity. Our results suggest that alphas1-Casein may be a potential biomarker for early identification of BPH patients.

Adenocarcinoma↗

PubMed2004

Id-I stimulates cell proliferation through activation of EGFR in ovarian cancer cells.

Increased EGFR (epidermal growth factor receptor) expression has been reported in many types of human cancer and its levels are positively associated with advanced cancers. Recently, upregulation of Id-1 (inhibitor of differentiation or DNA binding) protein was found in over 70% of ovarian cancer samples and correlated with poor survival of ovarian cancer patients. However, the molecular mechanisms responsible for the role of Id-1 in ovarian cancer are not clear. The aim of this study was to investigate the effect of Id-1 on ovarian cancer proliferation and its association with the EGFR pathway. To achieve this, we transfected an Id-1 expression vector into three ovarian cancer cell lines and examined cell proliferation rate by flow cytometry and bromodeoxyuridine staining. We found that ectopic Id-1 expression led to increased cell proliferation demonstrated by increased BrdU incorporation rate and S-phase fraction. The Id-1-induced cell growth was associated with upregulation of EGFR at both transcriptional and protein levels. In contrast, inactivation of Id-1 through transfection of an Id-1 antisense vector resulted in downregulation of EGFR. Our results indicate that increased Id-1 in ovarian cancer cells may promote cancer cell proliferation through upregulation of EGFR. Our findings also implicate that Id-1 may be a potential target for the development of novel strategies in the treatment of ovarian cancer.

Blotting, Western↗

PubMed2004

Id-1 expression and cell survival.

The Id (inhibitor of differentiation or DNA binding) helix-loop-helix (HLH) proteins are a group of dominant negative regulators of basic HLH transcriptional factors which promote cell differentiation. Recent evidence has revealed that Id proteins, especially Id-1, are also able to promote cell proliferation and cell cycle progression through inactivation of tumour suppressor and activation of growth promoting pathways in mammalian cells. In addition, upregulation of Id-1 has been found in many types of human cancer and its expression levels are also associated with advanced tumour stage. Furthermore, ectopic expression of Id-1 in human cancer cells is able to induce cell proliferation under sub-optimal conditions and protect the cells against apoptosis. These lines of evidence strongly indicate Id-1 as a positive regulator of cell growth and its expression may be a key factor required for tumour cell proliferation. This review will discuss recent evidence on the role of Id-1 in cell proliferation and survival, and its significance in malignant transformation. In addition, we will highlight the recent development in the understanding of the molecular mechanisms responsible for the action of Id-1 in promoting cell survival and tumourigenesis. Finally, the therapeutic implications through inactivation of Id-1 in the treatment of human cancer will also be addressed.

Animals↗