Cell cycle genes as targets of retinoid induced ovarian tumor cell growth suppression

Zhang, Dongmei; Vuocolo, Scott; Masciullo, Valeria; Sava, Teodoro; Giordano, Antonio; Soprano, Dianne Robert; Soprano, Kenneth J.

doi:10.1038/sj.onc.1204971

Cited by 38 publications

(37 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up-regulation of p53, p21 and other downstream genes may be one of the mechanisms of retinoid-response in ovarian cancer cells, as is seen in other cell lines. 51,52 A previous study has reported 52 that ovarian cancer cell lines that are sensitive to retinoic acid have a higher expression of p53, p27, p21 and p16 compared to the retinoid resistant lines, 52 which are concordant with our data. In OVCA433, which is sensitive to 4-HPR, there is an increase in p53, p21 and p16 expression in a dose-dependent manner, which correlates with growth inhibition and apoptosis.…”

Section: Discussionsupporting

confidence: 82%

4‐HPR modulates gene expression in ovarian cells

Brewer

Kirkpatrick

Wharton

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

Ovarian cancer has a high rate of recurrence and subsequent mortality following chemotherapy despite intense efforts to improve treatment outcomes. Recent trials have suggested that retinoids, especially 4-(N-hydroxyphenyl) retinamide (4-HPR), play an important role as a chemopreventive agent and are currently being used in clinical trials for ovarian cancer chemoprevention as well as treatment. This study examines the mechanism of its activity in premalignant and cancer cells.

show abstract

Section: Discussionsupporting

confidence: 82%

4‐HPR modulates gene expression in ovarian cells

Brewer

Kirkpatrick

Wharton

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Mitogenic stimulations are known to induce E2F activity and then to promote cyclin E gene expression that, in turn, positively regulates cell cycle progression. The regulation of cyclin E by RA appears to be a strong feature in monocytic cells, such as THP-1, while in other cell models, the regulation of cyclin D was more predominant [32,37].…”

Section: Discussionmentioning

confidence: 99%

“…4, the addition of physiological concentrations of RA to THP-1 cells significantly slowed down the G1/S transition as indicated by an increase in G1 phase cells, a decrease in S phase cells, and a reduction in cell proliferation rate. The regulation of Rb by RA has been noted in several cell models including lymphocytes and monocytes [32,37,56,57] and therefore may be a common element of RA-induced growth suppression in cells of various lineages and stages of differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…The ability of all-trans-RA to induce differentiation in multiple cell lines [36,37] and to inhibit tumorigenesis in human and animal studies [38] has led to its clinical use either alone or in combination with other therapeutics in the treatment of several types of malignancy, including acute myelocytic leukemia [39] and certain solid tumors [9,10]. Unraveling the underlying mechanisms that lead to retinoid-induced cell differentiation is an essential task for researchers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Retinoic acid regulates cell cycle progression and cell differentiation in human monocytic THP-1 cells

Chen

Ross

2004

Experimental Cell Research

View full text Add to dashboard Cite

All-trans-retinoic acid (RA), a natural metabolite of retinol, carries out most of the biological activities of vitamin A and is required for normal growth, cell differentiation, and immune functions. In the present studies, THP-1 human monocytes were used to investigate the mechanisms by which RA may regulate progression through the G1/S phase of the cell cycle. Physiological concentrations of all-trans-RA reduced the levels of cyclin E mRNA by 6 h and reduced cyclin E protein in a dose-and time-dependent manner. Similar reductions were observed for the retinoic acid receptor RAR and RXR proteins. Concomitantly, RA increased the level of the cyclin-dependent kinase inhibitor p27 (Kip-1). The levels of retinoblastoma mRNA and protein (pRb) were also increased, while the proportion of hyperphosphorylated (phosphoserine 807/811) pRb was markedly reduced. Overall, RA increased the functionality of pRb as an inhibitor of cell cycle progression. Furthermore, RA reduced the binding activity of the transcription factor E2F to its core DNA element. Retinoic acid-induced changes in cell cyclerelated proteins occurred in 4-6 h, including reduced cyclin E expression in bromodeoxyuridine (BrdU)-labeled cells, before the onset of cell differentiation as indicated by an increase in the percentage of G1 phase cells and a reduction in S phase cells at 24 h. The expression of CD11b, a cell surface marker of macrophage-like differentiation was increased by RA, as was phagocytic activity. The multiple effects of RA on cell cycle progression may help to explain its welldocumented ability to induce the differentiation of THP-1 cells, and thereby to enhance macrophage-like immune functions.

show abstract

“…Moreover, treatment of human embryonal carcinoma cells with all-trans-RA induced G 1 arrest through the accelerated ubiquitination of cyclin D1 (Spinella et al, 1999). Besides regulating the turnover of cyclins, retinoids were also shown to exert antiproliferative effects by modulating the levels of cyclin-dependent kinase (CDK) inhibitors, particularly of p21 WAF1/CIP1 (Liu et al, 1996;Li et al, 1998;Suzui et al, 2002) and p27 Kip1 (Pomponi et al, 1996;Zancai et al, 1998;Baldassarre et al, 2000;Hsu et al, 2000;Dow et al, 2001;Zhang et al, 2001;Dimberg et al, 2002). Nevertheless, the molecular mechanisms underlying these effects are still poorly defined.…”

Section: Introductionmentioning

confidence: 99%