OBJECTIVE: We recently described a new hormone @entity263 cell line, @entity37298 , derived from LNCaP via in vitro @entity342 deprivation. To study gene expression during @entity263 progression and to identify molecular targets for therapy, a pure @entity5 system was generated. METHODS: Limiting dilution of @entity37298 stably transfected with a green fluorescent protein, generated 35 single-cell clones, which were expanded into stable cell lines. In vitro responses to various therapeutic modalities were assessed in each clone. Gene expression was determined using reverse transcriptase-polymerase chain reaction and oligonucleotide microarrays. In vivo biology was assessed following orthotopic injection into intact and castrated severe combined immunodeficient @entity19 . RESULTS: In vitro, all clones demonstrated similar resistance to traditional therapeutic efforts including chemotherapy and radiation therapy, but differential sensitivity to cell-mediated @entity137 . The clones demonstrated differential gene expression relative to each other and to the parental @entity37298 and LNCaP cell lines. Following orthotopic injection into @entity19 , three distinct growth patterns were observed: fast growth with widespread @entity3 ; slower grower with widespread @entity3 ; and no @entity5 formation. Using oligonucleotide microarrays, several genes were identified as differentially expressed between the most @entity146 and the nontumorigenic clone. CONCLUSIONS: We have described a novel fluorescent-labeled @entity263 system that exhibited marked heterogeneity in its response to various therapeutic modalities, gene expression, and in vivo biology. Our data suggests that given the marked clonal heterogeneity, multi-modality approaches directed against multiple molecular targets rather than single agent therapy will be necessary to adequately eradicate the entire malignant cell population. @entity5 lines may allow more accurate examination of molecular pathways involved in @entity5 progression and resistance to treatment.

Heterogeneity of molecular targets on clonal cancer lines derived from a novel XXXX system.

@entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity263 :: ('MESH:D011471', 'Disease') :: ['refractory prostate cancer', 'clonal hormone refractory prostate cancer tumor', 'prostate cancer'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive'] @entity5 :: ('MESH:D009369', 'Disease') :: ['clonal tumor', 'tumor', 'Clonal tumor'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity37298 :: ('22859', 'Gene') :: ['CL1'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis']
@entity263 :: (MESH:D011471,Disease) :: ['hormone-refractory prostate cancer tumor']
