Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach

被引:42
作者
de Pinieux, G
Legrier, ME
Poirson-Bichat, F
Courty, Y
Bras-Gonçalves, R
Dutrillaux, AM
Némati, F
Oudard, S
Lidereau, R
Broqua, P
Junien, JL
Dutrillaux, B
Poupon, MF
机构
[1] Inst Curie, Sect Rech, UMR 147 CNRS, F-75231 Paris, France
[2] Hop Cochin, F-75674 Paris, France
[3] Ctr Rene Huguenin, St Cloud, France
[4] Lab Enzymol & Chim Prot, Tours, France
[5] Hop Europeen Georges Pompidou, Paris, France
[6] Ferring Res Inst Inc, San Diego, CA USA
关键词
D O I
10.1016/S0002-9440(10)61746-4
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
We report the clinical evolution of a prostate cancer, metastasizing to lungs and bones, recurring locally, and escaping from anti-androgen therapy. Key event of biological progression of the patient's tumor was the coincidence of allelic imbalance accumulation and of bone metastases occurrence. The recurrent tumor was established as the transplantable xenograft PAC120 in nude mice, where it grew locally. PAC120 displayed the same immunophenotype of the original tumor (positive for keratin, vimentin, prostatic acid phosphatase, and Leu-7) and expressed human HOXB9, HOXA4, HER-2/neu, and prostate-specific antigen genes, as detected by reverse transcriptase-polymerase chain reaction. it formed lung micrometastases detected by mRNA expression of human genes. Cytogenetic analysis demonstrated numerous alterations reflecting the tumor evolution. PAC120 was still hormone-dependent; its growth was strongly inhibited by the new gonadotropin-releasing hormone antagonist FE 200486 but weakly by gonadotropin-releasing hormone superagonist D-Trp(6)-luteinizing-hormone releasing hormone (decapeptyl). Tumor growth inhibition induced by anti-hormone therapy was linked to the hormone deprivation degree, more important and more stable with FE 200486 than with D-Trp(6)-luteinizing-hormone releasing hormone. Surgical castration of mice led to tumor regressions but did not prevent late recurrences. Transition to hormone-independent tumors was frequently associated with a mucoid differentiation or with a neuroendocrine-like pattern. independent variations of mRNA expression of HER-2/neu and prostate-specific antigen were observed in hormone-independent tumors whereas HOX69 gene expression was constant. In conclusion, PAC120 xenograft, a new model of hormone-dependent prostate cancer retained the progression potential of the original tumor, opening the opportunity to study the hormone dependence escape mechanism.
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收藏
页码:753 / 764
页数:12
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