Effect of Cyclin D1 Overexpression on Drug Sensitivity in a Human Fibrosarcoma Cell Line

Hochhauser, Daniel; Schnieders, Barbara; Ercikan-Abali, Emine A.; Görlick, Richard; Muise‐Helmericks, Robin C.; Li, Weiwei; Fan, Jun‐Yu; Banerjee, Debabrata; Bertino, Joseph R.

doi:10.1093/jnci/88.18.1269

Cited by 61 publications

(31 citation statements)

References 18 publications

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“…Alterations in expression of cell cycle regulators, such as E2F-1, cyclin/Cdks (cyclin Dl/Cdk4, cyclin A/Cdk2), and cyclin-dependent kinase (Cdk) inhibitors (p6, p21, and p27), play an important role in regulation of drug sensitivity (Hochhauser et al, 1996;St Croix et al, 1996;Li et al, 1997). NIH-OVCAR-3 cells that are deficient both in basal-and paclitaxel-induced p21 are associated with apoptotic resistance (Barboule et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Unique induction of p21WAF1/CIP1expression by vinorelbine in androgen-independent prostate cancer cells

et al. 2003

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To study the mechanisms of the development of hormone refractory prostate cancer, we established an androgen-independent (AI) prostate cancer cell line derived from hormone-dependent (AD) LNCaP cells. Our previous studies have demonstrated that AI cells are deficient in expression of p21 WAFl/CIP1 (p21) due to overexpressed AR and are resistant to apoptosis. In this study, the induction of p53 and p21 expression by vinorelbine (Navelbine) was compared between AD and AI cells in an attempt to understand the difference(s) in apoptotic signalling pathways in these cells. Using a series of deletion of p21 reporter constructs, we found that vinorelbine mediated p21 induction in a p53-dependent manner in AD cells. In contrast, p21 expression restored by vinorelbine in AI cells was found to be through both p53-dependent and-independent pathways. In the absence of two p53 binding sites, Spl-3 and Spl-4 sites, in the promoter of human p21 gene, were found to be required for vinorelbine-mediated p21 activation. No p21 induction was observed by paclitaxel in AI cells. Exposure of AI cells to paciltaxel followed by vinorelbine produced synergism. Our data, thus, provide a basis for the synergistic combination of vinorelbine and paclitaxel for the treatment of advanced prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Unique induction of p21WAF1/CIP1expression by vinorelbine in androgen-independent prostate cancer cells

et al. 2003

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“…Transfection of a cyclin DI -expressing plasmid was carried out as previously described (Hochhauser et al, 1996). Relative expression of cyclin Dl mRNA ratios were 14.4 and 0.48 for the high-and low-expression clones, whereas the comparable cyclin Dl expression ratios were 2.88 and 0.9 as compared with the vector-only-transfected control (Hochhauser et al, 1996).…”

Section: Materials and Methods Cell Culturementioning

confidence: 99%

Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells

Ligueros

Jeoung²,

Tang³

et al. 1997

Br J Cancer

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Summary The antiproliferative effects of gossypol on human MCF-7 mammary cancer cells and cyclin Dl-transfected HT-1060 human fibrosarcoma cells were investigated by cell cycle analysis and effects on the cell cycle regulatory proteins Rb and cyclin Dl. Flow cytometry of MCF-7 cells at 24 h indicated that 10 gm gossypol inhibited DNA synthesis by producing a G,/S block. Western blot analysis using antihuman Rb antibodies and anti-human cyclin Dl antibodies in MCF-7 cells and high-and low-expression cyclin Dl-transfected fibrosarcoma cells indicated that, after 6 h exposure, gossypol decreased the expression levels of these proteins in a dose-dependent manner. Gossypol also decreased the ratio of phosphorylated to unphosphorylated Rb protein in human mammary cancer and fibrosarcoma cell lines. Gossypol (10 gM) treated also decreased cyclin D1-associated kinase activity on histone Hi used as a substrate in MCF-7 cells. These results suggest that gossypol might suppress growth by modulating the expression of cell cycle regulatory proteins Rb and cyclin Dl and the phosphorylation of Rb protein.

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“…Recent data suggest a possible link between cell cycle alterations and the emergence of resistance to specific anticancer agents, although the molecular mechanisms underlying such correlation still need to be elucidated (Hochhauser et al, 1996;Eymin et al, 1999).…”

mentioning

confidence: 99%

Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts

et al. 2003

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Cell cycle progression in eukaryotic cells is regulated by a family of cyclin-dependent kinases (CDKs). Cyclin E is a regulatory subunit of CDK2 and drives cells from G1 to S phase. Increased expression of cyclin E is a frequent event in human malignancies and has been associated with poor prognosis in various cancers. In this study, we evaluated the effects of cyclin E-overexpression on the sensitivity of rat fibroblasts to anticancer drugs. Cyclin E-overexpressing cells were less sensitive to doxorubicin-induced inhibition of cell growth but not to other antineoplastic drugs, such as paclitaxel, vincristine, etoposide and methotrexate. Cyclin E-overexpressing fibroblasts also displayed a reduction in ROS levels and a significantly lower increase following doxorubicin treatment compared with vector control cells. The expression of manganese superoxide dismutase (MnSOD) and its activity were increased (about 1.3-fold) in cyclin E-overexpressing derivatives compared with control cells. These results suggest that cyclin E overexpression might reduce tumour cells sensitivity to doxorubicin by affecting the expression of MnSOD and that determination of cyclin E expression levels might help to select patients to be treated with an anthracycline-based antineoplastic therapy.

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Effect of Cyclin D1 Overexpression on Drug Sensitivity in a Human Fibrosarcoma Cell Line

Cited by 61 publications

References 18 publications

Unique induction of p21WAF1/CIP1expression by vinorelbine in androgen-independent prostate cancer cells

Unique induction of p21WAF1/CIP1expression by vinorelbine in androgen-independent prostate cancer cells

Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells

Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts

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