A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells.

A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides -6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progresses rapidly to local invasion. Metastases to lymph nodes, liver, lung, and bone are common by 6 months. Tumorigenesis is not dependent on androgens. This model indicates that the neuroendocrine cell lineage of the prostate is exquisitely sensitive to transformation and provides insights about the significance of neuroendocrine differentiation in human prostate cancer.

[1]  J. Gordon,et al.  Examining the Role of Paneth Cells in the Small Intestine by Lineage Ablation in Transgenic Mice* , 1997, The Journal of Biological Chemistry.

[2]  K Remberger,et al.  Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. , 1995, Human pathology.

[3]  R. Matusik,et al.  Prostate cancer in a transgenic mouse. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[4]  U. Stein,et al.  Multidirectional differentiation in the normal, hyperplastic, and neoplastic human prostate: simultaneous demonstration of cell-specific epithelial markers. , 1994, Human pathology.

[5]  D. Bostwick,et al.  Intraductal dysplasia: a premalignant lesion of the prostate. , 1986, Human pathology.

[6]  P. Scardino,et al.  Elevated plasma chromogranin-A concentrations in prostatic carcinoma. , 1991, The Journal of urology.

[7]  C. Perez-stable,et al.  Prostate, adrenocortical, and brown adipose tumors in fetal globin/T antigen transgenic mice. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[8]  David G. Bostwick,et al.  High grade prostatic intraepithelial neoplasia. The most likely precursor of prostate cancer , 1995 .

[9]  M. Lieberman,et al.  The use of antibodies to 5-bromo-2'-deoxyuridine for the isolation of DNA sequences containing excision-repair sites. , 1984, The Journal of biological chemistry.

[10]  J. Green,et al.  Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Rosen,et al.  Metastatic prostate cancer in a transgenic mouse. , 1996, Cancer research.

[12]  M. Selsted,et al.  Paneth cell defensins: Endogenous peptide components of intestinal host defense , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  H. Bonkhoff.  Role of the basal cells in premalignant changes of the human prostate: a stem cell concept for the development of prostate cancer. , 1996, European urology.

[14]  P. Wingo,et al.  Cancer statistics, 1996 , 1996, CA: a cancer journal for clinicians.

[15]  W. Rayford,et al.  Calcitonin stimulates growth of human prostate cancer cells through receptor-mediated increase in cyclic adenosine 3',5'-monophosphates and cytoplasmic Ca2+ transients. , 1994, Endocrinology.

[16]  R. Cohen,et al.  BCL-2 proto-oncogene expression in prostate cancer and its relationship to the prostatic neuroendocrine cell. , 1994, Archives of pathology & laboratory medicine.

[17]  M. Kattan,et al.  Androgen-independent prostate cancer progression in the TRAMP model. , 1997, Cancer research.

[18]  A. Angelsen,et al.  Neuroendocrine cells in the prostate of the rat, guinea pig, cat, and dog , 1997, The Prostate.

[19]  C. Logothetis,et al.  Small cell carcinoma of the prostate part I a clinicopathologic study of 20 cases , 1987, Cancer.

[20]  R. Cohen,et al.  The neuroendocrine cell population of the human prostate gland. , 1993, The Journal of urology.

[21]  Guan Wu,et al.  Parathyroid hormone-related protein: a potential autocrine growth regulator in human prostate cancer cell lines. , 1994, Urology.

[22]  J. Montie,et al.  Trends in the stage specific incidence of prostate carcinoma in the Detroit metropolitan area: 1973‐1994 , 1996, Cancer.

[23]  J. Ward,et al.  Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations. , 1996, Cancer research.

[24]  L. Grimelius,et al.  The course of neuroendocrine differentiation in prostatic carcinomas. An immunohistochemical study testing chromogranin A as an "endocrine marker". , 1989, Pathology, research and practice.

[25]  U. Stein,et al.  The proliferative function of basal cells in the normal and hyperplastic human prostate , 1994, The Prostate.

[26]  P. A. Sant'agnese,et al.  Neuroendocrine differentiation in human prostatic carcinoma , 1992 .

[27]  P. di Sant'Agnese,et al.  Neuroendocrine differentiation in prostatic malignancy , 1996, Cancer.

[28]  R. Cohen,et al.  Neuro-endocrine cells--a new prognostic parameter in prostate cancer. , 1991, British journal of urology.

[29]  M. Ciomei,et al.  Bombesin stimulates growth of human prostatic cancer cells in vitro , 1990, Cancer.

[30]  H. Bonkhoff,et al.  Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: A stem cell model , 1996, The Prostate.