A novel human cancer culture model for the study of prostate cancer

Yasunaga, Yutaka; Nakamura, Keiichiro; Ko, Daejin; Srivastava, Shiv; Moul, Judd W.; Sesterhenn, Isabell A.; McLeod, David G.; Rhim, Johng S.

doi:10.1038/sj.onc.1205002

Cited by 43 publications

(57 citation statements)

References 28 publications

(40 reference statements)

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“…It is interesting to note that 4q alteration observed in both cell lines is the change also observed chromosome change in an established human prostate cancer cell line derived from primary tumor of a familial prostate cancer patient (5). Possible evidence of a prostate cancer susceptibility locus on chromosome 4q has been reported (16).…”

Section: Discussionmentioning

confidence: 99%

“…Nonmalignant cells were derived from non-cancerous regions that were confirmed by histopathological examination. The method for generating primary prostate cell cultures has been described (5). Briefly, the tumor and non-malignant tissue obtained by an experienced pathologist was chopped into small fragments, 1-2 mm in size with a sterile blade.…”

Section: Generation Of Primary Cell Culturesmentioning

confidence: 99%

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Establishment and characterization of a pair of non-malignant and malignant tumor derived cell lines from an African American prostate cancer patient

Theodore

Sharp²,

Zhou³

et al. 2010

Int J Oncol

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Abstract.Research into molecular and genetic mechanisms underlying prostate carcinogenesis in high-risk African American men would be greatly advanced by in vitro models of African American prostate tumors representing primary tumors. However, the generation of immortalized primary African American prostate cancer cells that will accurately reflect the in situ characteristics of malignant epithelium is currently limited but is greatly needed. We have successfully established immortalized cell lines of a pair of non-malignant and malignant tumors derived from an African American prostate cancer patient with HPV-16E6E7 (RC-77N/E and RC-77T/E). RC-77N/E and RC-77T/E cells are currently growing well at passage 40. Both cells exhibit epithelial morphology and are androgen sensitive. The RC-77T/E cells produced tumors in SCID mice whereas the RC-77N/E cells produced no tumor in SCID mice. These cells expressed androgen-regulated prostate-specific homobox gene, NKX 3.1, epithelial cell specific cytokeratn 8, androgen receptor (AR), prostate specific antigen (PSA), and p16. Chromosome analysis showed that both cell lines are similar; near diploid human male (XY) with most chromosome counts in the 45-48 range. However, RC-77T/E cell line has new marker chromosomes: M1B=del/t(4;?)(q28;?), M5=16q+ in addition to those observed in the RC-77N/E cell line (M1=del(4)(q28q34)+hsr in some, M1A=t(4q;?),M2=der(9?),M2A=del(M2p-),M3=iso(?), M4=der(22?)). This is the first documented case of the establishment of pair of non-malignant and malignant tumors derived from an African American prostate cancer patient. These models will provide novel tools to study the molecular and genetic mechanisms of prostate carcinogenesis, especially for high-risk African American men.

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Section: Discussionmentioning

confidence: 99%

Section: Generation Of Primary Cell Culturesmentioning

confidence: 99%

Establishment and characterization of a pair of non-malignant and malignant tumor derived cell lines from an African American prostate cancer patient

Theodore

Sharp²,

Zhou³

et al. 2010

Int J Oncol

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“…IBC-10a and PCa-20a cells were primary intermediate basal cell lines derived from human prostate cancer by our laboratory (18). The IBC10a cells were immortalized by transfections with LXSNhTERT retroviral vector (courtesy of Johng Rhim, Center for Prostate Disease Research, USUHS, Bethesda, MD), using methods previously described (19). IBC-10a and PCa-20a cells were found to be CK5 and CK18 positive and are classified as intermediate basal cells (18).…”

Section: Cell Culturesmentioning

confidence: 99%

Role of Ribosomal Protein RPS2 in Controlling let-7a Expression in Human Prostate Cancer

Wang

Hu²,

Amatangelo³

et al. 2011

Molecular Cancer Research

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We discovered that an inverse relationship exists in the expression of ras/c-myc and ribosomal protein RPS2 with pre-let-7a-1/let-7a/let-7f miRNA and prostate tumor cell malignancy. Nonmalignant IBC-10a cells expressed low levels of ras/RPS2 and elevated pre-let-7a-1/let-7a/let-7f miRNA, whereas the reverse occurred in malignant PCa-20a and PC-3ML cells. Stable transfection of IBC-10a cells with pBABE.ras and pBABE.RPS2 induced ras, c-myc, and RPS2 expression, whereas the levels of let-7a/let-7f miRNA dropped to near zero. Conversely, in pBABE.pre-let-7a-1 transfected PCa-20a and PC-3ML clones, let-7a/let-7f increased whereas ras, RPS2, and c-myc dropped greater than 5-fold. Electrophoretic mobility shift assays, antibody "supershift" assays and immunoprecipitation assays revealed that RPS2 specifically binds pre-let-7a-1 to block RNA processing. Immunoflourescent studies and Northern blots confirmed that RPS2 complexes with pre-let-7a-1 (i.e., in episomal structures) to block processing to let-7a/let-7f, indicating RPS2 may prevent let-7a miRNA expression to indirectly promote oncogene expression. Functional studies further showed that the colony-forming ability (CFA) and invasive activities of IBC-10a cells were significantly enhanced in pBABE-ras.IBC-10a and pBABE-RPS2-IBC-10a clones. Conversely, with the "knockdown" of ras and RPS2 in malignant PC-3ML cells (i.e., in pLKO. TRC.shRNA.ras.PC3-ML, pLKO.TRC.shRNA.RPS2.PC-3ML transfected cells), there was both a loss of these functions and a loss of tumorigenesis in SCID mice. Likewise, with the overexpression of let-7a/let-7f in pBABE. pre-let-7a-1.PC-3ML clones (and PCa-20a clones), CFAs, invasive activities in vitro, and tumorigenesis in vivo were significantly reduced. These results show for the first time that RPS2 blocks pre-let-7a-1 processing to enable ras and c-myc expression and the transformation of primary tumor cells. Mol Cancer Res; 9(1); 36-50. Ó2011 AACR.

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“…Tumor tissue on gross inspection was dissected separately for the purpose of generating a cell culture. The method for generating primary cell cultures has been previously described (25,26). Briefly, minced pieces of tissues were distributed to several collagen-coated cell culture dishes with keratinocyte serum-free medium (K-SFM) (Life Technologies, Inc., Gaithersburg, MD) supplemented with 5% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

“…To investigate potential biological differences in epithelial cells in ethnic populations, we established primary cell cultures from prostate tumors resected from AA and EA men as described (25,26). Cultured cells, showing typical epithelial cell morphology were selected for gene expression profiling (14 AA and 13 EA cell cultures).…”

Section: Survival Migration and Invasion Genes Are Upregulated In Prmentioning

confidence: 99%

Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men

Dritschilo¹

2009

Int J Oncol

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Abstract. African-American (AA) men experience an increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with the potential to predispose AA men to prostate tumor progression and metastasis. To identify cancer-specific gene expression patterns in AA men, we established primary prostate cancer epithelial cells from 14 AA and 13 EA men. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. Quantitative RT-PCR and immunohistochemistry validated mRNA and protein expression levels. RNAi knockdowns provided support for biological significance for the identified genes in prostate cancer cells. Son of sevenless homolog 1 (SOS1) was overexpressed in AA male-derived primary prostate cancer epithelial cells. Depletion of SOS1 in PC3 and DU145 prostate cancer cells resulted in decreased capacities for cell proliferation, migration and invasion, at least partially through inhibition of extracellular signal-regulated kinase 1 and 2. Tissue microarray analyses of SOS1 expression in prostate carcinomas correlated with Gleason's grades of tumors, consistent with a possible role in prostate cancer progression. Investigation of prostate cancer-derived epithelial cells has led to identification of SOS1 as a potential candidate biomarker and molecular therapeutic target in prostate cancer in AA men, consistent with the hypothesis that a biological basis exists for prostate cancer aggressiveness in AA men.

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A novel human cancer culture model for the study of prostate cancer

Cited by 43 publications

References 28 publications

Establishment and characterization of a pair of non-malignant and malignant tumor derived cell lines from an African American prostate cancer patient

Establishment and characterization of a pair of non-malignant and malignant tumor derived cell lines from an African American prostate cancer patient

Role of Ribosomal Protein RPS2 in Controlling let-7a Expression in Human Prostate Cancer

Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men

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