Sensitivity to cis‐diamminedichloroplatinum in human cancer cells is related to expression of cyclin D1 but not C‐RAF‐1 protein

Abstract

can be upregulated by the myc or ras oncogenes, we also chose to study putative relationships between cyclin D I protein levels and intrinsic cellular sensitivity to CDDP and y-irradiation. We report that in the 16 human cell lines which we have studied, high cyclin DI expression is related to CDDP resistance but has no relationship with radiation responsiveness, whereas high c-raf-I expression, although related to radiosensitivity has no relationship with CDDP responsiveness.

Inhibition of Myc-dependent apoptosis by eukaryotic translation initiation factor 4E requires cyclin D1

“…A compelling link between D cyclins and induction of apoptosis is provided by direct gain of cyclin D1 function studies in cell systems where overexpressed cyclin D promoted ectopic cell cycle transit (Hiyama and Reeves, 1999;Kranenburg et al, 1996;Sofer-Levi and Resnitzky, 1996). Mitigating this are the data in this report along with other investigations utilizing direct gain-and-loss of D cyclin function in lymphoid cells (Rhee et al, 1995;Warenius et al, 1996), cells from pancreatic carcinoma (Kornmann et al, 1997) and lung cancer cells (Driscoll et al, 1999). Moreover, recent ®ndings demonstrate that transcriptional upregulation of endogenous cyclin D1 by activating its promoter, inhibits apoptosis (Albanese et al, 1999), whereas antisense cyclin D1 induces apoptosis and decreases tumor size in human squamous carcinomas (Sauter et al, 1999).…”

“…Enforced expression of cyclin D1 in quiescent, post-mitotic neurons (Kranenburg et al, 1996), growth restricted ®broblasts (Sofer-Levi and Resnitzky, 1996), or irradiated ®broblasts (Pardo et al, 1996) stimulates cell cycle entry and leads to apoptosis. However, in cells ectopically expressing strong growth promoters, such as Myc and Ras, high levels of D-cyclins (cyclins D1, D2, and D3) rescue cells from apoptosis induced by dexamethasone (Rhee et al, 1995) or cytotoxic drugs (Warenius et al, 1996). In addition, inhibition of cyclin D1 sensitizes lung cancer cells to apoptosis when serum survival factors are withdrawn (Driscoll et al, 1999).…”

Late G1 accumulation after 2 Gy of γ-irradiation is related to endogenous Raf-1 protein expression and intrinsic radiosensitivity in human cells

“…Protein estimations were performed and the final concentration of the lysates adjusted to 150 mg of total cellular protein per 100 ml. Rafl, Myc, Ras, Cdk4, Cyclin Dl and Actin proteins were analysed by SDS-PAGE electrophoresis as previously described (Warenius et al, 1994b(Warenius et al, , 1996b. Two independent Westem immunoblottings using separately prepared lysates for each cell line loaded in pairs on each electrophoretic gel were carried out.…”

“…Two independent Westem immunoblottings using separately prepared lysates for each cell line loaded in pairs on each electrophoretic gel were carried out. Conditions were optimized for each protein measured, and linearity studies at different protein loadings were made to confirm quantitation on Westem blotting (Warenius et al, 1996b;Browning, 1997). Then, 50-150 mg of total cellular protein in 50 ml of lysate buffer were added per lane well to 7.5-15% Laemmli separating gels as appropriate for each of the relevant proteins, and electrophoresis was carried out at 16'C using 60 V over 16 h and a constant current of 500 mA.…”

A role for intracellular immunization in chemosensitization of tumor cells?

“…Tumor cells can acquire drug resistance via several distinct mechanisms, including altered glutathione metabolism, 1 increased DNA repair mechanism, 2,3 altered topoisomerase activity, 4,5 and increased expression of the MDR1 gene product. [6][7][8][9][10][11][12][13][14] In addition, alterations in the expression of various oncogenes, such as Bcl-2, [15][16][17][18][19] p53, 18,[20][21][22] and cyclin D1, 23,24 and growth factor receptors, not only can lead to the perturbation of growth regulation but may also affect the sensitivity of tumor cells to conventional chemotherapy. [25][26][27][28][29][30][31][32][33][34] The delineation of some of the genetic determinants involved in drug resistance has enabled the development of new gene therapy-based strategies to overcome this important clinical problem.…”