A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer

Węgiel, Barbara; Bjartell, Anders; Ekberg, Jenny; Gadaleanu, Virgil; Brunhoff, Cecilia; Persson, Jenny L.

doi:10.1038/sj.onc.1208795

Cited by 52 publications

(66 citation statements)

References 38 publications

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“…In the present review, we focus on the regulation and function of VEGFA (also referred to as simply VEGF) in angiogenesis. VEGF is overexpressed in a variety of hematological malignancies (Krejsgaard et al 2006) and the vast majority of solid tumors, including PCa (Wegiel et al 2005) (Fig. 1), where it is associated with poorer outcomes (Duque et al 1999, Green et al 2007.…”

Section: Transcriptional Regulation Of Pro-angiogenesis Pathways In Pcamentioning

confidence: 99%

“…Following local recurrence and metastasis, androgen deprivation therapy (ADT), which is achieved medically or through orchiectomy, is typically effective for !24 months, by which time progression to the more detrimental form of castrateresistant PCa (CRPC) is common . At that point, PCa becomes hormone refractory, and cancer cells acquire the ability to invade and metastasize to lymph nodes and distant organs (Wegiel et al 2005).…”

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confidence: 99%

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Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

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Section: Transcriptional Regulation Of Pro-angiogenesis Pathways In Pcamentioning

confidence: 99%

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confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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“…A functional pRb protein is necessary for cyclin A1 to induce the autocrine expression of VEGF in prostate cancer, through an upregulation in VEGF promoter activity (Wegiel et al, 2005).…”

Section: Involvement Of Rb Family In Angiogenesis C Gabellini Et Almentioning

confidence: 99%

Involvement of RB gene family in tumor angiogenesis

Gabellini¹,

Bufalo²,

Zupi³

2006

Oncogene

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Angiogenesis, the development of new blood vessels from pre-existing vessels, represents a fundamental step in tumor progression and metastatization. The induction of vasculature is required for growth of the tumor mass, to ensure an adequate supply of oxygen and metabolites to the tumor beyond a critical size. Tumor angiogenesis is a highly regulated process that is controlled physiologically by the tumor microenvironment and genetically by alteration of several oncogenes or tumor suppressor genes. We will focus on recent demonstrations regarding the involvement of the retinoblastoma family proteins (phosphorylated retinoblastoma (pRb), p107 and pRb2/p130) at different levels of the angiogenic process. pRb and its homologs can regulate the expression of pro-and antiangiogenic factors, such as the vascular endothelial growth factor, through an E2F-dependent mechanism. Moreover, pRb is able to modulate also the transcriptional activity of several angiogenesis-related factors like HIF-1, Id2 and Oct-1. pRb2/p130 is required for both differentiation and mobilization of bone marrow-derived endothelial cell precursors and endothelial sprouting from neighboring vessels. The involvement of the pRb pathway in the angiogenesis process has also been demonstrated by different cellular models expressing viral oncoproteins, like human papilloma virus. Moreover, some natural and synthetic compounds demonstrate their antiangiogenetic activity with a mechanism of action involving pRb. Finally, the possible prognostic value of immunohistochemical evaluation of pRb and/or pRb2/p130 expression can represent a useful tool for the characterization of the angiogenic phenotype of specific tumor histotypes.

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“…Cyclin A1 is an important cell-cycle regulator and its expression is elevated in prostate cancer (46,47). It acts as a coregulator of AR on VEGF promoter activity to regulate VEGF expression (46,47).…”

Section: Introductionmentioning

confidence: 99%

Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow

et al. 2016

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Bone metastasis is a leading cause of morbidity and mortality in prostate cancer. While cancer stem-like cells have been implicated as a cell of origin for prostate cancer metastasis, the pathways that enable metastatic development at distal sites remain largely unknown. In this study, we illuminate pathways relevant to bone metastasis in this disease. We observed that cyclin A1 (CCNA1) protein expression was relatively higher in prostate cancer metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase (CYP19A1), a key enzyme that directly regulates the local balance of androgens to estrogens. Cyclin A1 overexpression in the stem-like ALDH high subpopulation of PC3M cells, one model of prostate cancer, enabled bone marrow integration and metastatic growth. Further, cells obtained from bone marrow metastatic lesions displayed self-renewal capability in colonyforming assays. In the bone marrow, cyclin A1 and aromatase enhanced local bone marrow-releasing factors, including androgen receptor, estrogen and matrix metalloproteinase MMP9 and promoted the metastatic growth of prostate cancer cells. Moreover, ALDH high tumor cells expressing elevated levels of aromatase stimulated tumor/host estrogen production and acquired a growth advantage in the presence of host bone marrow cells. Overall, these findings suggest that local production of steroids and MMPs in the bone marrow may provide a suitable microenvironment for ALDH high prostate cancer cells to establish metastatic growths, offering new approaches to therapeutically target bone metastases. Cancer Res; 76(8); 2453-64. Ó2016 AACR.

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A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer

Cited by 52 publications

References 38 publications

Regulation of vascular endothelial growth factor in prostate cancer

Regulation of vascular endothelial growth factor in prostate cancer

Involvement of RB gene family in tumor angiogenesis

Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow

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