Expression of BCL-2 Oncoprotein and P53 Protein Accumulation in Bone Marrow Metastases of Androgen Independent Prostate Cancer

McDonnel, Timothy J.; Navone, Nora M.; Troncoso, Patricia; Pisters, Louis L.; Conti, Claudio J.; Eschenbach, Andrew C. von; Brisbay, Shawn; Logothetis, Christopher J.

doi:10.1097/00005392-199702000-00042

Cited by 21 publications

(21 citation statements)

References 14 publications

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“…29,37 Also, it is worth noting that an enforced expression of bcl-2 causes a more invasive phenotype in LNCaP cells. 38,39 Hence, there is a desperate need to discover a non-androgen ablative means to kill the androgen-insensitive cancer cells of the prostate which do over-express these apoptosis suppressor proteins. In this regard, several important publications have revealed the fact that, despite offering resistance to several apoptotic stimuli such as androgen withdrawal, serum starvation or phorbol ester treatment, androgen-insensitive prostate cancer cells do in fact maintain the basic and apparently functional apoptotic machinery which could be activated under certain circumstances.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of curcumin in human prostate cancer—I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells

Dorai

Gehani

Katz

2000

Prostate Cancer Prostatic Dis

110

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In an effort to ®nd an alternative nontoxic means of inducing the apoptosis potential in both androgen-dependent and hormone refractory prostate cancer cells, attention was focused on curcumin (turmeric), traditionally used in medicine and cuisine in India and other south-east Asian countries. The results indicate that curcumin is a novel and potent inducer of apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. This was accomplished by down-regulating apoptosis suppressor proteins and other crucial proteins such as the androgen receptor. It is concluded that curcumin may provide an alternative, nontoxic modality by which the clinician may prevent the progression of prostate cancer to its hormone refractory state or to treat advanced prostate cancer by forcing them to undergo apoptosis. Prostate Cancer and Prostatic Diseases (2000) 3, 84±93.

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Section: Discussionmentioning

confidence: 99%

Therapeutic potential of curcumin in human prostate cancer—I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells

Dorai

Gehani

Katz

2000

Prostate Cancer Prostatic Dis

110

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“…Levels of the antiapoptotic oncoprotein, Bcl-2, increase during the ®rst 3 months of NHT, and remain elevated after 8 months of therapy, 49 consistent with its role in prevention of castration-induced apoptosis. 51,52 Taken together, ongoing decreases in serum PSA, the high percentage of organ-con®ned and small-volume tumors, and the absence of increased PCNA and Ki-67 immunostaining suggest that progression from outgrowth of androgen-independent clones during prolonged NHT is unlikely.…”

Section: Does Tumor Progression Occur During Prolonged Nht?mentioning

confidence: 99%

Neoadjuvant hormonal therapy prior to radical prostatectomy: promises and pitfalls

Gleave

Bianca

Goldenberg

2000

Prostate Cancer Prostatic Dis

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“…One of the antiapoptotic factors that favors the survival of androgen-refractory prostate cancer cells may involve overexpression of Bcl-2 (McDonnell et al, 1992;Colombel et al, 1993;Krajewska et al, 1996). Bcl-2 protein is expressed intensely in 77% of androgen-refractory prostate tumors compared to 32% in androgen-sensitive tumors (McDonnell et al, 1992(McDonnell et al, , 1997Westin et al, 1995).…”

mentioning

confidence: 99%

Androgens repress Bcl-2 expression via activation of the retinoblastoma (RB) protein in prostate cancer cells

et al. 2003

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The oncogene Bcl-2 is upregulated frequently in prostate tumors following androgen ablation therapy, and Bcl-2 overexpression may contribute to the androgen-refractory relapse of the disease. However, the molecular mechanism underlying androgenic regulation of Bcl-2 in prostate cancer cells is understood poorly. In this study, we demonstrated that no androgen response element (ARE) was identified in the androgen-regulated region of the P1 promoter of Bcl-2 gene, whereas, we provided evidence that the androgenic effect is mediated by E2F1 protein through a putative E2F-binding site in the promoter. We further demonstrated that retinoblastoma (RB) protein plays a critical role in androgen regulation of Bcl-2. The phosphorylation levels of RB at serine residues 780 and 795 were decreased in LNCaP cells treated with androgens. Ectopic expression of a constitutively active form of RB inhibited expression of Bcl-2. Knockdown of endogenous RB protein by an Rb small inference RNA (siRNA) induced an increase in Bcl-2 levels. Most importantly, the effect of androgens on Bcl-2 was abolished completely by specific inhibition of RB function with a mutated E1A. Finally, androgen treatment of LNCaP cells upregulated specifically levels of the cyclindependent kinase inhibitors (CDKIs) p15INK4B and p27KIP1. Ectopic expression of p15INK4B and/or p27KIP1 inhibited Bcl-2 expression. Knockdown of endogenous p15INK4B or p27KIP1 protein with a pool of siRNAs diminished androgen-induced downregulation of Bcl-2 expression. Therefore, our data indicate that androgens suppress Bcl-2 expression through negatively modulating activities of the E2F site in the Bcl-2 promoter by activating the CDKI-RB axis.

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Expression of BCL-2 Oncoprotein and P53 Protein Accumulation in Bone Marrow Metastases of Androgen Independent Prostate Cancer

Cited by 21 publications

References 14 publications

Therapeutic potential of curcumin in human prostate cancer—I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells

Therapeutic potential of curcumin in human prostate cancer—I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells

Neoadjuvant hormonal therapy prior to radical prostatectomy: promises and pitfalls

Androgens repress Bcl-2 expression via activation of the retinoblastoma (RB) protein in prostate cancer cells

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