Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle

Matsushime, Hitoshi; Roussel, Martine F.; Ashmun, Richard A.; Sherr, Charles J.

doi:10.1016/0092-8674(91)90101-4

Cited by 1,139 publications

(784 citation statements)

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“…Cyclin D1 and cdc2 are required for the progression of cells from the G1 phase to the S-phase of the cell cycle [22,23], and guggulsterone suppressed the expression of both of them in a time-dependent manner in U937 cells. The expression of the cyclin-dependent kinase inhibitors p21 WAF1/CIP1 and p27, which block cell cycle progression by inhibiting the activity of cyclin/Cdk2 complexes, was also upregulated by guggulsterone.…”

Section: Discussionmentioning

confidence: 99%

“…Because D-type cyclins and cyclin-dependent kinases are required for the progression of cells from the G1 phase to the S-phase of the cell cycle [22,23], we determined the effect of guggulsterone on cyclin D1 expression in U937 cells. We found that guggulsterone inhibited the expression of both cyclin D1 and cdc2 in a time-dependent manner (Fig 1D).…”

Section: Guggulsterone Inhibits the Expression Of Cell Cycle Regulatementioning

confidence: 99%

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Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products

Shishodia

Sethi

Ahn

et al. 2007

Biochemical Pharmacology

130

119

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Guggulsterone is a plant polyphenol traditionally used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, possibly through an anti-inflammatory mechanism. Whether this steroid has any role in cancer is not known. In this study, we found that guggulsterone inhibits the proliferation of wide variety of human tumor cell types including leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian carcinoma. Guggulsterone also inhibited the proliferation of drug-resistant cancer cells (e.g., gleevac-resistant leukemia, dexamethasone-resistant multiple myeloma, and doxorubicin-resistant breast cancer cells). Guggulsterone suppressed the proliferation of cells through inhibition of DNA synthesis, producing cell cycle arrest in S-phase, and this arrest correlated with a decrease in the levels of cyclin D1 and cdc2 and a concomitant increase in the levels of cyclin-dependent kinase inhibitor p21 and, p27. Guggulsterone induced apoptosis as indicated by increase in the number of Annexin V-and TUNEL-positive cells, through the down-regulation of anti-apoptototic products. The apoptosis induced by guggulsterone was also indicated by the activation of caspase 8, bid cleavage, cytochrome c release, caspase 9 activation, caspase 3 activation, and PARP cleavage. The apoptotic effects of guggulsterone were preceded by activation of JNK and down-regulation of Akt activity. JNK was needed for guggulsterone-induced apoptosis, inasmuch as inhibition of JNK by pharmacological inhibitors or by genetic deletion of MKK4 (activator of JNK) abolished the activity. Overall, our results indicate that guggulsterone can inhibit cell proliferation and induce apoptosis through the activation of JNK, suppression of Akt, and down-regulation of anti-apoptotic protein expression.

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Section: Discussionmentioning

confidence: 99%

Section: Guggulsterone Inhibits the Expression Of Cell Cycle Regulatementioning

confidence: 99%

Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products

Shishodia

Sethi

Ahn

et al. 2007

Biochemical Pharmacology

130

119

View full text Add to dashboard Cite

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“…Cyclin D1 was simultaneously identified by two groups; the first identified cyclin D1 in a subtractive screen for growth factor inducible genes (Matsushime et al, 1991) and the second group identified cyclin D1 through its ability to complement G1 cyclin loss in S. cerevisae (Xiong et al, 1991). These initial findings suggested that cyclin D1 harbors the capacity to modulate cell cycle progression.…”

Section: Introductionmentioning

confidence: 99%

Cyclin D1: polymorphism, aberrant splicing and cancer risk

et al. 2006

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The cyclin D1 proto-oncogene exercises powerful control over the mechanisms that regulate the mitotic cell cycle, and excessive cyclin D1 expression and/or activity is common in human cancers. Although somatic mutations of the cyclin D1 locus are rarely observed, mounting evidence demonstrates that a specific polymorphism of cyclin D1 (G/A870) and a protein product of a potentially related alternate splicing event (cyclin D1b) may influence cancer risk and outcome. Herein, we review the epidemiological and functional literatures that link these alterations of cyclin D1 to human tumor development and progression.

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“…In particular, a role of cyclin D1 in G1 progression has been clearly shown in numerous independent studies (Baldin et al, 1993;Quelle et al, 1993;Jiang et al, 1993). Expression of mammalian D-and E-type cyclins as well as CDK4 can be induced in G1 by mitogens or growth factors and their continuous synthesis depends on the persistence of a mitogenic stimulus (Matsushime et al, 1991;Sewing et al, 1993Sewing et al, , 1994. Overexpression of both D-and E-type cyclins shortens progression through G1 in a number of di erent mammalian cell types tested (Jiang et al, 1993;Resnitzky et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Mutual requirement of CDK4 and Myc in malignant transformation: evidence for cyclin D1/CDK4 and p16INK4A as upstream regulators of Myc

Haas

Staller²,

Geisen

et al. 1997

Oncogene

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We demonstrate in this paper that CDK4 which is a G1 phase speci®c cell cycle regulator and catalytic subunit of D-type cyclins has oncogenic activity similar to Dtype cyclins themselves and is able to provoke focus formation when cotransfected with activated Ha-ras into primary rat embryo ®broblasts. Surprisingly, using two di erent mutants we show that CDK4's ability to bind to p16 INK4a and not its kinase activity is important for its transforming potential. In addition, p16 INK4a but not a mutant form that is found in human tumours can completely abrogate focus formation by CDK4 suggesting that CDK4 can malignantly transform cells by sequestering p16 INK4a or other CKIs. We demonstrate that both cyclin D1 and CDK4 functionally depend on active Myc to exert their potential as oncogenes and vice versa that the transforming ability of Myc requires functional cyclin D/CDK complexes. Moreover, we ®nd that p16 INK4a and the Rb related protein p107 which releases Myc after phosphorylation by cyclin D1/CDK4 e ciently block Myc's activity as a transcriptional transactivator and as an oncogene. We conclude that both p16 INK4a and cyclin D/CDK4 complexes are upstream regulators of Myc and directly govern Myc function in transcriptional transactivation and transformation via the pocket protein p107.

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Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle

Cited by 1,139 publications

References 73 publications

Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products

Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products

Cyclin D1: polymorphism, aberrant splicing and cancer risk

Mutual requirement of CDK4 and Myc in malignant transformation: evidence for cyclin D1/CDK4 and p16INK4A as upstream regulators of Myc

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