Cyclin D1 protein was expressed at relatively high levels in all of the six human prostate cancer cell lines examined, but was not detected in the cultures of normal human prostate cells.
In order to investigate factors involved in human prostate cancer progression, we studied the effects of cyclin D1 overexpression on human prostate cancer cell proliferation and tumorigenicity by transfecting LNCaP cells with a retroviral vector containing human cyclin D1 cDNA.
Taken together, these data establish the potency of cyclin D1 as an AR corepressor and provide support for additional studies examining the efficacy of developing novel prostate cancer therapies for both androgen-dependent and -independent tumors.
However, the AA genotype of CCND1 showed a tendency to increase prostate cancer risk in subjects aged 70 years or older (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 0.86-5.27, p = 0.096).
Taken together, bombesin-induced cyclin D1 expression in prostate cancer cells is mediated by Egr-1 activation and the interaction of Egr-1 with the Egr-1/Sp1 motif of the cyclin D1 promoter through the activation of MAPK pathway.
These data demonstrate that differential cyclin D1 status may influence clinicopathological parameters, and reveal new insight as to the regulation and potential consequence of cyclin D1 expression in prostate cancer.
We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis.
This study provides a molecular basis to support the correlation of IL-8 expression with that of cyclin D1 in human prostate cancer and suggests a mechanism by which this chemokine promotes cell proliferation.
This study provides a molecular basis to support the correlation of IL-8 expression with that of cyclin D1 in human prostate cancer and suggests a mechanism by which this chemokine promotes cell proliferation.
Exisulind in combination with celecoxib modulates epidermal growth factor receptor, cyclooxygenase-2, and cyclin D1 against prostate carcinogenesis: in vivo evidence.
Together, our data indicate that PGG induced PCa S-arrest probably through DNA replicative blockage and induced G(1) arrest via cyclin D1 downregulation to contribute to anticancer activity.
Galectin-3 knockdown in human prostate cancer PC3 cells led to cell-cycle arrest at G(1) phase, up-regulation of nuclear p21, and hypophosphorylation of the retinoblastoma tumor suppressor protein (pRb), with no effect on cyclin D1, cyclin E, cyclin-dependent kinases (CDK2 and CDK4), and p27 protein expression levels.
Our results identify Sam68 as the first splicing factor to affect CCND1 alternative splicing in prostate cancer cells, and suggest that increased levels of Sam68 may stimulate cyclin D1b expression in human prostate cancers.
Therefore, deregulation of CCND1 may be a major cause of cisplatin resistance in testicular germ cell tumors and may also be implicated in ovarian and prostate cancers.
Mining of publicly available human prostate cancer oligoarray datasets revealed that the expression of numerous genes (e.g., CCND1, CD44) under the control of beta-catenin transcription is down-regulated.
In the present study, we investigated the diagnostic value of 3 different genes associated with CaP carcinogenesis, encoding for cell cycle (MDM2, CCND1) and apoptotic (Fas) genes that are differentially expressed in CaP.
Prostate cancer was used as a paradigm because this tumor type is reliant at all stages of the disease on androgen receptor (AR) signaling, and cyclin D1 has been shown to negatively modulate AR-dependent expression of prostate-specific antigen (KLK3/PSA).
Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines.
These findings suggest that CCND1 expression is possibly regulated by estrogens via ERβ and that this signaling pathway may influence prostate cancer development.