| Publication number |
CLPUB00483 |
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| Authors |
Rhim J.S., Li H.-Z., Furusato B., Miki J., Sun C., Sreenath T., Dobi A., Petrovics G., Hukku B., Sesterhenn I.A., McLeod D.G., Srivastava S. |
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| Title |
A new cell line expressing a novel type of TMPRSS2-ERG gene fusion derived from primary tumors of familial prostate cancer patient. |
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| Citation |
Cancer Res. 68 Suppl. 9:194-194(2008) |
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| Web pages |
https://aacrjournals.org/cancerres/article/68/9_Supplement/194/545672/ |
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| Abstract |
Recent studies have established that a high proportion of prostate cancer
harbors a gene fusion between the androgen regulated TMPRSS2 gene and the
ETS genes ERG, ETV1 or ETV4. However in vitro model representing primary
tumors to study the molecular mechanisms and functional consequences of
this important chromosomal rearrangement are currently limited and are
greatly needed. The tumor tissue (RC-123T) used for generating the
RC-123T/E cell line with HPV-16 E6E7 genes was obtained from a 57 year old
familial prostate cancer patient who had adenocarcinoma with well
differentiation (Gleason 3+3). The cell line was characterized
phenotypically and cytogenically. Dual color fluorescence in situ
hybridization (FISH) assay was used to test for ERG (3'5') break aparts,
and for translocation of TMPRSS2 and ERG and ETV1, in both interphase
nuclei as well as metaphases. The cells were also characterized for
putative stem cell markers CD133, SOX2 and prostate cell markers by
immunohistochemistry and RT-PCR. We have successfully established an
immortalized human prostate epithelial cell culture derived from primary
tumors of familial prostate cancer patients carrying TMPRSS2-ERG fusion
genes with HPV16 E6E7 genes (RC-123T/E). RC-123T/E cells are currently
growing well at passage 30, whereas RC-123T cells senesced at passage 5.
Expression of an androgen-regulated prostate specific homeobox gene, NKX3.
1, the epithelial cell-specific cytokeratin 8 and androgen receptor but
not prostate specific antigen, was detected in RC-123T/E cells. TMPRSS2-
ERG genes were also expressed in this line. The RC-123T/E cells formed
spheres under suspension culture and branched differentiated in matrigel.
The RC-123T/E cells also expressed putative stem cell markers CD133 and
SOX2. Interestingly, the FISH analysis showed the translocation of
chromosome t(7;21)(q21:q21) in the RC-123T/E cell line and also in its
primary tumor tissue. We demonstrate that RC-123T/E cell line and its
primary tumor tissue possess the translocation of TMPRSS2/ERG to
chromosome 7q which adds another class of gene arrangement in prostate
cancer. In addition, this cell line expressed putative stem cell markers
and TMPRSS2-ERG gene fusion. This model provides a novel tool to study the
cellular and molecular mechanisms of TMPRSS2-ETS genes in prostate cancer.
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| Cell lines |
CVCL_VV24; RC-123T/E |
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