Protein Profiling of Microdissected Prostate Tissue Links Growth Differentiation Factor 15 to Prostate Carcinogenesis

Cheung, Peter K.; Woolcock, Bruce W.; Adomat, Hans; Sutcliffe, Margaret; Bainbridge, Terry C.; Jones, Edward C.; Webber, Douglas; Kinahan, Thomas J.; Sadar, Marianne D.; Gleave, Martin; Vielkind, Juergen R.

doi:10.1158/0008-5472.can-04-1216

Cited by 94 publications

(79 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is well known that protein expression profiles differ both between tumours with different histopathologic grades (Ware et al, 2003;Iwadate et al, 2004) and between different tumour stages (Cheung et al, 2004;Roblick et al, 2004). However, to our knowledge, the finding that the tumour protein expression profile changes over time in histologically identical tumours is novel.…”

Section: Discussionmentioning

confidence: 99%

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

et al. 2006

View full text Add to dashboard Cite

Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12 Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation -time of flight -mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches.

show abstract

Section: Discussionmentioning

confidence: 99%

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

et al. 2006

View full text Add to dashboard Cite

show abstract

“…For instance, RANKL down-regulated genes encoding proteasome 26S and ribophorin I, known to reduce the proteasomal degradation machinery (24,25) and GDF-15 that is associated with early prostate carcinogenesis (26). In addition, RANKL upregulated NF-IB which is potentially implicated in cell morphology and susceptibility to nuclear oncogenes (27).…”

Section: Discussionmentioning

confidence: 99%

Receptor activator of nuclear factor-κB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells

Mori¹,

Berreur²,

Blanchard³

et al. 2007

Oncol Rep

View full text Add to dashboard Cite

Abstract. Receptor activator of nuclear factor κB (RANK)/ RANK ligand (RANKL)/osteoprotegerin (OPG) are the key regulators of bone metabolism. Recent findings demonstrated a crucial role of RANK in several bone-associated tumors. Indeed, we have recently demonstrated functional RANK expression both in a mouse and several human osteosarcoma cell lines. However, RANKL effects on osteosarcoma cells remain to be determined. In this study, we determined RANKL effects on RANK-positive Saos-2 human osteosarcoma cells. cDNA microarray and quantitative RT-PCR analyses clearly demonstrated that RANK-positive osteosarcoma cells were the target of RANKL as well as osteoclasts/osteoclast precursors. Thus, we present for the first time that RANKL can directly and significantly modulate gene expression of RANK-expressing Saos-2 cells. RANKL-modulated genes included genes that were implicated in protein metabolism, nucleic acid metabolism, intracellular transport, cytoskeleton organization and biogenesis, apoptosis and signaling cascade. Our results strengthen the involvement of the RANK/RANKL/OPG axis in osteosarcoma biology and capability to identify novel therapeutic approaches targeting RANK-positive osteosarcomas.

show abstract

“…Although previous proteomic studies on prostate cancer have identified a number of alterations associated with the development of cancer (Ahram et al, 2002;Meehan et al, 2002;Schulz et al, 2003;Cheung et al, 2004), studies aimed specifically at identifying protein alterations associated with the metastatic progression are limited. A recent study has compared the protein profile of a highly metastatic human prostate cancer cell line M12 with its poorly tumorigenic variant M12(F6), and identified a reduced level of vimentin in the poorly tumorigenic variant (Liu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer

et al. 2006

View full text Add to dashboard Cite

In order to identify novel candidates associated with prostate cancer metastasis, we compared the proteomic profile of the poorly metastatic human prostate cancer cell line LNCaP, with its highly metastatic variant LNCaP-LN3, by two-dimensional gel electrophoresis. A major protein spot (pI of 5.9 and molecular weight of 37 kDa) was seen in LNCaP cells, but not in LNCaP-LN3 cells and was identified as lactate dehydrogenase-B (LDHB), by tandem mass spectrometry. Furthermore, enzyme kinetic assays and zymography showed a higher LDH enzyme activity in LNCaP cells compared with LNCaP-LN3. Bisulphite-modified DNA sequencing showed promoter hypermethylation in LNCaP-LN3 cells but not in LNCaP, Du145, PC3, CWR22 or BPH45 cells. Treatment of LNCaP-LN3 cells with 5 0 -azacytidine caused reexpression of LDHB transcripts. In tissues, LDHB promoter hypermethylation occurred at a higher frequency in prostate cancer, 14/ 31 (45%), compared to adjacent nonmalignant or benign tissue, 2/19 (11%) (Po0.025). Immunohistochemistry showed a higher frequency of LDHB expression in benign or nonmalignant tissues, 59/ 73 (81%), compared to cancer cases, 3/53 (6%) (Po0.001). Absent LDHB expression was also seen in 7/7 (100%) cases of metastatic cancer in bone. Our data are the first to show loss of LDHB expression in prostate cancer, the mechanism of which appears to involve promoter hypermethylation.

show abstract

Protein Profiling of Microdissected Prostate Tissue Links Growth Differentiation Factor 15 to Prostate Carcinogenesis

Cited by 94 publications

References 15 publications

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

Receptor activator of nuclear factor-κB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells

Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer

Contact Info

Product

Resources

About