73 Cytogenetic characterization of androgen-responsive and -unresponsive sublines of the human prostatic carcinoma cell line LNCAP

König, Josée J.; Kamst, Eric; Hagemeijer, Anne; Horoszewicz, Julius S.; Schröder, Fritz H.

doi:10.1016/0165-4608(89)90600-6

Cited by 7 publications

(9 citation statements)

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“…Thus, the basic karyotype of the original cell line was well preserved. Duplication of the marker M1, interpreted as a der(1) t(1;15) (p22.3; q24), was found also in other LNCaP sublines that were established during in vitro propagation (Konig et al, 1989). Data from those cell lines suggest that duplication of this marker is rather a result of cytogenetic evolution during long-term in vitro culture than a specific response of LNCaP cells to androgen-free conditions.…”

Section: Discussionmentioning

confidence: 72%

“…Cytogenetic analysis of the parental human prostate cancer cell line LNCaP used in this study revealed essentially the karyotype of the cell line originally developed by Horoszewicz et al (1983) and chromosomally characterized by Gibas et al (1984) and Konig et al (1989). Thus, the basic karyotype of the original cell line was well preserved.…”

Section: Discussionmentioning

confidence: 76%

“…Both the parental cells and the LNCaP-abl subline had the same basic karyotype. This was essentially a near tetraploid karyotype with the consistent diploid markers M1 to M9 as reported by Gibas et al (1984) and Konig et al (1989). Three additional chromosomal changes compared to this basic karyotype were found in the LNCaP-abl subline: (i) an additional copy of marker M1 was present in LNCaP-abl cells; (ii) a new marker chromosome was formed from one copy of M8 (4q+); and (iii) a partial or complete loss of the Y-chromosome was observed (see also Table 2).…”

Section: Ar Sequence and Cytogenetic Analysismentioning

confidence: 91%

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Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system

Hoffmann²,

et al. 1999

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Advanced prostate cancer is treated by androgen ablation and/or androgen receptor (AR) antagonists. In order to investigate the mechanisms relevant to the development of therapy-resistant tumours, we established a new tumour model which closely resembles the situation in patients who receive androgen ablation therapy. Androgen-sensitive LNCaP cells were kept in androgen-depleted medium for 87 passages. The new LNCaP cell subline established in this manner, LNCaP-abl, displayed a hypersensitive biphasic proliferative response to androgen until passage 75. Maximal proliferation of LNCaP-abl cells was achieved at 0.001 n M of the synthetic androgen methyltrienolone (R1881), whereas 0.01 n M of this compound induced the same effect in parental cells. At later passages (> 75), androgen exerted an inhibitory effect on growth of LNCaP-abl cells. The non-steroidal anti-androgen bicalutamide stimulated proliferation of LNCaP-abl cells. AR protein expression in LNCaP-abl cells increased approximately fourfold. The basal AR transcriptional activity was 30-fold higher in LNCaP-abl than in LNCaP cells. R1881 stimulated reporter gene activity in LNCaP-abl cells even at 0.01 n M , whereas 0.1 n M of R1881 was needed for induction of the same level of reporter gene activity in LNCaP cells. Bicalutamide that acts as a pure antagonist in parental LNCaP cells showed agonistic effects on AR transactivation activity in LNCaP-abl cells and was not able to block the effects of androgen in these cells. The non-steroidal AR blocker hydroxyflutamide exerted stimulatory effects on AR activity in both LNCaP and LNCaP-abl cells; however, the induction of reporter gene activity by hydroxyflutamide was 2.4- to 4-fold higher in the LNCaP-abl subline. The changes in AR activity were associated neither with a new alteration in AR cDNA sequence nor with amplification of the AR gene. Growth of LNCaP-abl xenografts in nude mice was stimulated by bicalutamide and repressed by testosterone. In conclusion, our results show for the first time that the non-steroidal anti-androgen bicalutamide acquires agonistic properties during long-term androgen ablation. These findings may have repercussions on the natural course of prostate cancer with androgen deprivation and on strategies of therapeutic intervention. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 76%

Section: Ar Sequence and Cytogenetic Analysismentioning

confidence: 91%

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Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system

Hoffmann²,

et al. 1999

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“…Deletions of 8p were first described in association with development of androgen resistance in the prostate carcinoma cell line LNCaP [2]. Subsequently, many allelotyping studies have shown 8p LOH in the majority of tumors analyzed.…”

Section: Introductionmentioning

confidence: 97%

Isochromosome 8q formation is associated with 8p loss of heterozygosity in a prostate cancer cell line

et al. 1999

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“…Since collagenase is a widely used enzyme for tissue disaggregation, especially in tumor cytogenetics, the presented data will have consequences for the interpretation of results obtained by methods involving the use of this enzyme. Key terms: Solid tumor cytogenetics, DNA flow cytometry, DNA aneuploidy, tissue disaggregation Solid tumor cytogenetics comprises a small but rapidly expanding field of research, A number of reports on the cytogenetics of prostate carcinoma (PC) have indicated several structural chromosome rearrangements, which are thought to be possibly tumor specific (1,7,8,14). However, the majority of the investigated PC specimens (73%) demonstrate a surprising lack of both structural and numerical chromosomal changes, resulting in essentially normal diploid karyotypes (3,8,141.…”

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confidence: 99%

Preferential loss of abnormal prostate carcinoma cells by collagenase treatment

König¹,

Dongen²,

Schröder³

1993

Cytometry

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Effects of two different methods of tumor disaggregation on flow cytometric ploidy distribution and intact cell yield were investigated. Either mechanical disaggregation or collagenase digestion was applied to 35 prostate tumor specimens. Seven collagenase-treated samples failed to yield any intact cells, whereas with mechanical disaggregation in all cases a sufficient number of intact cells were obtained. No differences in the FCM ploidy distribution of tumors with a DNA diploid stemline were observed comparing both techniques. In DNA aneuploid tumors, however, collagenase treatment had an adverse effect on the abnormal cell populations. In 14/17 of such tumors, the abnormal cell populations were significantly reduced; in eight of these the percentage of DNA aneuploid cells declined even below the minimum percentage (10%) that was defined for DNA aneuploidy. Since collagenase is a widely used enzyme for tissue disaggregation, especially in tumor cytogenetics, the presented data will have consequences for the interpretation of results obtained by methods involving the use of this enzyme.

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73 Cytogenetic characterization of androgen-responsive and -unresponsive sublines of the human prostatic carcinoma cell line LNCAP

Cited by 7 publications

References 0 publications

Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system

Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system

Isochromosome 8q formation is associated with 8p loss of heterozygosity in a prostate cancer cell line

Preferential loss of abnormal prostate carcinoma cells by collagenase treatment

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