Specific Receptors for Vitamin D3 in Human Prostatic Carcinoma Cells

Miller, Gary J.; Stapleton, Gary; Houmiel, Kathryn L.; Ferrara, Janet A.

doi:10.1007/978-1-4615-3704-5_23

Cited by 4 publications

(5 citation statements)

References 18 publications

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“…This effect is similar to that observed in monolayer cultures (Table I), and is in agreement with previous studies utilizing whole fetal bovine serum [6,20,31]. This inhibition of growth should not be con-fused with the growth-stimulatory effect observed in the presence of charcoal-stripped serum [6,21].…”

Section: Hormonal Regulation Of Monolayer Growth Is Not Indicative Ofsupporting

confidence: 92%

“…Our laboratory previously showed that monolayer cultures of the ALVA-31 and LNCaP cell lines are the most responsive to the growth-regulatory properties of 1␣,25(OH) 2 vitamin D 3 (1,25(OH) 2 D 3 ) and androgens of the seven human PC cell lines analyzed [20][21][22][23][24][25]. In the current study, we tested a spheroid cell culture system for its ability to enhance the effects of these hormones on the growth and differentiation of the same seven cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Three-dimensional spheroid cultures of human prostate cancer cell lines

1999

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BACKGROUND Many of the available human prostate cancer (PC) cell lines have lost androgen sensitivity and no longer secrete prostate‐specific proteins after serial culturing in cell monolayers. Three‐dimensional spheroid cultures have been found to better mimic the in vivo phenotypes of several nonprostatic cell lines. METHODS We analyzed seven PC cell lines to determine if spheroid culturing results in greater sensitivity to androgens and 1α,25(OH)2 vitamin D3 (1,25(OH)2 D3) with regards to their growth, differentiation, and apoptotic potential. RESULTS Only PC‐3 cells showed greater sensitivity to the growth‐inhibitory effects of 1,25(OH)2 D3, while ALVA‐31 showed a diminished response. The regulation of prostate‐specific antigen and prostate‐specific acid phosphatase remained unchanged. However, these studies provided several unique findings not observed in cell monolayers. First, three basic spheroid morphologies were observed with varying degrees of intercellular adhesions. Secondly, the cell lines that formed the tightest spheroids consistently grew at the slowest rates, regardless of their growth rate in monolayers. Lastly, 1,25(OH)2 D3 treatment of ALVA‐31 and PPC‐1 spheroids greatly reduced intercellular adhesions, and rendered ALVA‐31 spheroids resistant to apoptotic induction by Fas ligand expressed via a recombinant adenoviral construct. CONCLUSIONS Our results suggest that spheroid cultures of human PC cells may provide unique insights regarding cell adhesion and apoptotic potential that are diminished or absent in monolayer cultures. Prostate 41:154–165, 1999. © 1999 Wiley‐Liss, Inc.

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Section: Hormonal Regulation Of Monolayer Growth Is Not Indicative Ofsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Three-dimensional spheroid cultures of human prostate cancer cell lines

1999

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“…Furthermore, 1,25-VD inhibited LNCaP cell growth when the cells were cultured in FBS-containing medium, but no effect was observed in charcoal-stripped FBScontaining medium (Miller et al, 1992;Zhao et al, 1997). The growth inhibitory effect was restored by cotreating the cells with 1,25-VD and a low concentration of androgen in charcoal-stripped FBS medium.…”

Section: Introductionmentioning

confidence: 93%

“…Even though these cells express similar levels of functional VDRs, they respond to 1,25-VD-mediated inhibitory effects differently. For example, LNCaP, an androgen-dependent prostate cancer cell line, is significantly inhibited by 1,25-VD; however, the PC-3, DU 145, and ALVA-31 cell lines are less sensitive to the antiproliferative action mediated by 1,25-VD (Miller et al, 1992;Schwartz et al, 1994;Miller et al, 1995;Blutt et al, 1997). These results suggest that VDR expression is not solely responsible for the growth suppression induced by 1,25-VD (Skowronski et al, 1993;Zhuang et al, 1997;Zhuang and Burnstein, 1998).…”

Section: Introductionmentioning

confidence: 99%

Androgen signaling is required for the vitamin D-mediated growth inhibition in human prostate cancer cells

Bao

Ting

et al. 2004

Oncogene

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Epidemiological data on prostate cancer incidence has suggested that vitamin D deficiency may be a risk factor for prostate cancer. The antiproliferative activity of 1a, 25-dihydroxyvitamin D 3 (1,25-VD) and its analogues has been demonstrated in many prostate cancer models, yet the detailed mechanisms underlying this protective effect of vitamin D remain to be determined. Here, we demonstrate that two androgen receptor (AR)-positive prostate cancer cell lines, LNCaP and CWR22R, are more sensitive to the growth inhibitory effects of 1,25-VD compared to the AR-negative prostate cancer cell lines, PC-3 and DU 145. 1,25-VD treatment inhibited cyclindependent kinase 2 (cdk2) activity and induced G0/G1 arrest. Interestingly, we also found that 1,25-VD treatment induced the expression of AR, and that the onset of the G0/G1 arrest in LNCaP and CWR22R cells is correlated with the onset of increasing expression of AR. This implies that the antiproliferative actions of 1,25-VD in AR-positive prostate cancer might be mediated through AR. Furthermore, a reduction in 1,25-VD-mediated growth inhibition was observed when AR signaling was blocked by antiandrogens, AR RNA interference, or targeted disruption of AR. Taken together, our data suggest that the androgen/AR signaling plays an important role in the antiproliferative effects of 1,25-VD and restoration of androgen responsiveness by 1,25-VD might be beneficial for the treatment of hormone-refractory prostate cancer patients.

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“…For example, the ALVA-31 cell line was derived from a well-differentiated adenocarcinoma, while JCA-1 and PPC-1 were derived from poorly differentiated adenocarcinomas. Also of interest is that these apoptotic potentials do not appear to be related to steroid hormone sensitivity, since ALVA-31 and LNCaP show the greatest growth regulation by androgens [17,34] and 1,25-dihydroxyvitamin D 3 [35] of the 7 cell lines. …”

Section: Correlation Of Tumor Stage With Sensitivity To Fas Signalingmentioning

confidence: 99%