Alterations in the expression of the cell cycle regulators, cyclin D1 and cyclin-dependent kinase 4 (Cdk4), have been implicated in malignancies of both humans and experimental animal models. We hypothesize that altered expression of cyclin D1 and Cdk4 may also be involved in mouse colon tumorigenesis induced by the chemical carcinogen, azoxymethane (AOM). In the present study, SWR/J mice were ...

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates the pRB protein and promotes G1/S cell-cycle progression and oncogenesis. Dicer is a central regulator of miRNA maturation, encoding an enzyme that cleaves double-stranded RNA or stem-loop-stem RNA into 20-25 nucleotide long small RNA, governing sequence-specific gene silencing and heterochromatin methylation. The mech...

Cyclin D1 is known as a proto-oncogene whose gene amplification and protein overexpression are frequently observed in tumor cells. It acts as a mitogenic signal sensor and is expressed as a delayed-early response to many mitogenic signals. Cyclin-dependent kinases (CDKs) 4 and 6 are cyclin D1 binding partners, and activated cyclin D1/CDK4 and cyclin D1/CDK6 complex phosphorylate the retinoblast...

SSeCKS, first isolated as a G(1)-->S inhibitor that is downregulated in src- and ras-transformed cells, is a major cytoskeleton-associated PKC substrate with tumor suppressor and kinase-scaffolding activities. Previous attempts at constitutive expression resulted in cell variants with truncated ectopic SSeCKS products. Here, we show that tetracycline-regulated SSeCKS expression in NIH 3T3 cells...

In mantle cell lymphoma, the t(11;14)(q13;q32) and its molecular counterpart, bcl-1 rearrangement, are consistent features and lead to cyclin D1 (bcl-1, PRAD1) proto-oncogene overexpression. In order to detect cyclin D1 overexpression, we developed a simple assay involving a reverse transcription followed by competitive polymerase chain reaction (PCR). A single upstream primer was derived from ...

In light of the clinical relevance of targeting cyclin D1 in breast cancer, we have investigated the mechanism underlying the effect of the peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists troglitazone and ciglitazone on cyclin D1 repression. We obtain evidence that the ability of high doses of troglitazone and ciglitazone to repress cyclin D1 is independent of PPARgamma ac...

Iron (Fe) plays an important role in proliferation, and Fe deficiency results in G(1)/S arrest. Despite this, the precise role of Fe in cell-cycle control remains unclear. Cyclin D1 plays a critical function in G(1) progression by interacting with cyclin-dependent kinases. Previously, we examined the effect of Fe depletion on the expression of cell-cycle control molecules and identified a marke...

Cyclin D1 is a target for positive regulation by estrogens in growth-responsive cells, in which it mediates their mitogenic effects. Amplification and overexpression of the cyclin D1 gene (CCND1) might thus represent a genetic lesion inducing hormone-independent growth of transformed cells. Indeed, cyclin D1 overexpression has been found in up to 50% of primary breast cancers, and in about one-...

BACKGROUND Pituitary tumors are a common form of endocrine neoplasia. However few studies assessed the expression of the principal cyclin regulating checkpoint exit, cyclin D1. Cyclin D1 expression in pituitary tumors and its possible relation to MIB-1 and p27/Kip1 labeling indices (LIs) was explored. DESIGN We studied a total of 199 pituitaries, including normal pituitaries (n=7), pituitary ...

The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate cyclin-dependent kinase 4-mediated phosphorylation of pRB in the cell cycle of normal cells. p16/CDKN2 gene and cyclin D1/PRAD-1 gene alterations have been detected in squamous cell carcinoma cell lines and in several primary squamous cell carcinomas of the esophagus. We immunohistochemically assessed p16 and cyclin D1...