Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells

Abstract

TTRAP is a multi-functional protein that is involved in multiple aspects of cellular functions including cell proliferation, apoptosis and the repair of DNA damage. Here, we demonstrated that the lentivirus-mediated overexpression of TTRAP significantly inhibited cell growth and induced apoptosis in osteosarcoma cells. The ectopic TTRAP suppressed the growth and colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2. Cell apoptosis was induced in U2OS cells and the cell cycle was arrested at G2/M phase in Saos-2 cells. Exogenous expression of TTRAP in serum-starved U2OS and Saos-2 cells induced an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression. In comparison with wild-type TTRAP, mutations in the 5'-tyrosyl-DNA phosphodiesterase activity of TTRAP, in particular TTRAPE152A, showed decreased inhibitory activity on cell growth. These results may aid in clarifying the physiological functions of TTRAP, especially its roles in the regulation of cell growth and tumorigenesis. [BMB Reports 2013; 46(2): 113-118]

An internal ribosome entry site in the coding region of tyrosyl-DNA phosphodiesterase 2 drives alternative translation start

“…1, D and E). Although our sample size is limited, our data suggests that expression of the shorter isoform of TDP2 is correlated with decreased proliferation upon TDP2 depletion, and confirms previously published data that the effects of TDP2 knockdown are cell-line dependent (6,7).…”

“…TDP2 is well documented as a DNAdamage preventing phosphodiesterase, and has been reported to interact with both growth and apoptotic pathways (3)(4)(5)(6)33) in different contexts. In NSCLC, TDP2 facilitates proliferation and tumor growth (6), whereas overexpression of TDP2 in osteosarcoma cell lines such as U2OS and Saos-2 correlate with decreased proliferation and increased apoptosis (7). A key question to ask would be how TDP2 can switch between these opposing functions.…”

“…Furthermore, increased cytoplasmic immunohistochemical staining of TDP2 has been correlated to NSCLC disease stage in patient samples (6). Conversely, in osteosarcoma cell lines, such as U2OS and Saos-2, which normally express low levels of TDP2, overexpressing TDP2 causes decreased proliferation in culture, reduced colony formation, increased caspase activation, and G 2 /M phase cell cycle stalling (7).…”

Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells

“…Among them, G 0 /G 1 and G 2 /M phases are important check point in apoptotic cell. If there is any DNA damage the cell are not proceeding to the next generation and thus the life cycle of the cell is terminated (24 , 25) .…”

Emerging Cytokine Networks in Osteosarcoma

“…Special emphasis must be placed on the role of emerging cytokine networks in immunoregulatory and coordinating functions [3] . Bone destruction and pathological bone formation are crucial features in the natural course of osteosarcoma [23] , which implies that several cytokines must be involved in the pathogenesis of these tumours. While the effects of autocrine and paracrine signalling of some cytokines and other growth factors on established osteosarcoma cell lines have been demonstrated [24,25,26,27] , knowledge of the cytokine expression in osteosarcoma remains limited, and little is known about the contribution of cytokines to osteosarcoma progression [9] .…”