Abstract
N-myc downstream regulated gene 1 (NDRG1), also known as differentiation related gene 1, was previously identified as an up-regulated gene upon cellular differentiation. Even though its sequence along with its expressional pattern in cancer cell lines are evident, the functional aspects concerning cell proliferation, viability, differentiation and cell cycle regulation of NDRG1 remains vague. The aim of the present study was to elucidate the functional role of NDRG1 in human prostate cancer. Our results showed basal levels of NDRG1 expression in PC-3 (poorly differentiated, null p53), DU-145 (moderately differentiated, mutant p53) and LNCaP (well-differentiated, wiled type p53). Nevertheless, NDRG1 sequencing assay disclosed no mutations in the gene. Furthermore, human cDNA of NDRG1 from normal placenta was cloned into a eukaryotic expression vector and transfected into the three cancer cell lines. This resulted in over-expression of NDRG1, which in turn markedly up regulated two differentiation markers of the prostate tissue, p21 and cytokeratin 8/18. Unpredictably, cell cycle progression, cell proliferation and DNA synthesis were unaffected following NDRG1 expression. These results revealed that NDRG1 is functional in prostate cancer cells and able to induce expression of differentiation factors through p53 independent pathway. However, the pathway downstream NDRG1, involving p21 and c8/18, regulating cell cycle progression and DNA synthesis is unfunctional. Loss of sensitivity to p21 cell cycle control may be associated with prostatic cancer behavior. Further studies are required to clarify the intra cellular molecular pathways affecting NDRG1 function in human prostate cancer.
Highlights
Prostate cancer emerges as a central problem of male’s public health in recent years, as it develops mainly in elderly men making its incidence to be continuously growing in an era characterized with ageing of the population
To further investigate the functional role of N-myc downstream regulated gene 1 (NDRG1) in the prostatic cancer cells, the NDRG1 gene from normal human placenta biopsy, was cloned into a eukaryotic expression fected to the human prostate cancer cell lines
Its expression is induced by differentiation stimuli in cancer cells, and its up regulation in colon cancer cells induced morphological and molecular changes that were consistent with colon cancer cell line differentiation [10]
Summary
Prostate cancer emerges as a central problem of male’s public health in recent years, as it develops mainly in elderly men making its incidence to be continuously growing in an era characterized with ageing of the population. The development of prostate cancer is considered to be dependent on a number of gene abnormalities, and in this manner, the molecular biology research in this field is obvious and essential. NDRG1, a proliferation related gene, was investigated in order to clarify its functionality in human prostate cancer cells. Further studies revealed that NDRG1 is involved in carcinogenesis development, metastatic spreading, atherosclerosis, differentiation and cell survival [2]. This gene encodes a 43 kDa protein that contains three tandem repeats of 10 amino
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