OBJECTIVES To determine the duration of expression of the cell cycle regulators p21 and p16 and the effect of these 2 genes both alone and in combination on the growth of squamous cell carcinoma of the head and neck cell lines in vitro. EXPERIMENTAL METHODS AND DESIGN: Cells were transduced via an adenoviral vector with p21 (Ad5CMV-p21), p16 (Ad5CMV-p16), or both. Western blotting was performed...

The E7 oncoprotein of the high-risk human papillomaviruses (HPV) is thought to contribute to cervical carcinogenesis at least in part by abrogating cell cycle regulation. E7 can dysregulate the cell cycle through its interaction with several cellular proteins including the retinoblastoma suppressor protein pRb, as well as the cyclin-dependent kinase inhibitor p21(Cip1). Inactivation of pRb in c...

DNA endonuclease CtIP is involved in both DNA double-strand break (DSB) repair and transcriptional repression/activation. The cyclin-dependent kinase inhibitor P21, which is induced at transcription level in response to a variety of stresses, controls G₁/S transition. In this report, we found that CtIP bound to the P21 promoter, and this binding was enhanced in response to DNA damage. Concomita...

How the p53 transcription factor/tumor suppressor inhibits cell invasion is poorly understood. We demonstrate that this function of p53 requires its direct interaction with p21(WAF1), a transcriptional target of p53, and that both p21 and p53 bind to Slug, which promotes cell invasion. Functional studies reveal that p21 and p53 cooperate to facilitate Mdm2-dependent Slug degradation and that th...

Inositol hexaphosphate (IP6) causes G(1) arrest and increases cyclin-dependent kinase inhibitors p21/Cip1 and p27/Kip1 protein levels in human prostate cancer (PCa) DU145 cells lacking functional p53. However, whether cyclin-dependent kinase inhibitor I induction by IP6 plays any role in its antitumor efficacy is unknown. Herein, we observed that either p21 or p27 knockdown by small interfering...

PURPOSE The peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-dependent transcription factor belonging to the family of nuclear receptors, has been implicated in the regulation of cell growth and differentiation although the exact mechanism(s) of this activity has not been elucidated. In this study, we explored the role of PPARgamma signaling on the control of gene expressi...

MXDs are transcription repressors that antagonize MYC-mediated gene activation. MYC, when associated with MIZ1, acts also as a repressor of subset genes, including p15 and p21. A role for in regulation MYC-repressed genes is not known. We report activate p21 U2OS cells. This activation required DNA binding by their interaction MIZ1. MXD mutants deficient MIZ1 interacted the MYC-binding partner ...

Purpose: The peroxisome proliferator-activated receptor (PPAR ), a ligand-dependent transcription factor belonging to the family of nuclear receptors, has been implicated in the regulation of cell growth and differentiation although the exact mechanism(s) of this activity has not been elucidated. In this study, we explored the role of PPAR signaling on the control of gene expression of the cycl...

Although p21 WAF1/Cip1 expression has been detected immunohistochemically in non-small cell lung cancer (NSCLC), the associations between p21 expression and clinical characteristics are unknown. To determine the association between p21 expression and clinical features, p21 expression was immunohistochemically analyzed in paraffin-embedded tumor samples from 137 patients with curatively resected...

Chelators such as 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311) and di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) target tumor cell iron pools and inhibit proliferation. These agents also modulate multiple targets, one of which is the cyclin-dependent kinase inhibitor, p21. Hence, this investigation examined the mechanism of action of these compounds in targeting p21....