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Ectopic expression of FGF-3 results in abnormal prostate and Wolffian duct development

Oncogene volume 21, pages 1899–1908 (2002)Cite this article

Abstract

To evaluate the effects of FGF-3 expression in the prostate and male reproductive tract, we employed a bitransgenic system to target FGF-3 to these organs. We present a first study that ectopic FGF-3 expression resulted in exuberant hyperplasia of all bigenic prostatic lobes typified by epithelial stratification, cribiform structures and papillary tufts. These cells displayed increased nuclear-to-cytoplasmic ratios and bromodeoxyuridine (BrdU) proliferative index but retained relatively uniform nuclear androgen receptor (AR) and the tumor suppressor C-CAM1 staining. Furthermore, the dysmorphogenic prostatic cells also resembled PIN (prostatic intraepithelial neoplasia)-like lesions but did not appear to have invaded the basal lamina. In addition to these phenotypes, profound disorders of the bigenic Wolffian duct derivatives were observed. The bigenic ampullary glands and vas deferens were extremely cystic, hypertrophic and hyperplastic; the enlarged epididymi showed a reduction of spermatozoa and the seminal vesicles exhibited a dramatic reduction of seminal secretions. Because of these severe abnormalities, these infertile males presented with diaphragmatic hernias, hemoperitoneum and many secondary abnormalities at sacrifice. Taken together, we show that ectopic FGF-3 expression severely perturbs normal prostate development and our system should be useful for the analyses of early changes in prostatic hyperplasia.

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Acknowledgements

We thank Drs Roberto Barrios, Barbara Foster, Paula Kaplan and Fred A Pereira for their valuable help, advice and critical discussions; Drs Brigid Hogan, Jay Chung and Susanne Mansour for their generous gift of the MMTV-KCR, HS4 insulator and murine FGF-3 plasmids respectively; Dr Phil Leder for the FGF-3 target mice and Dr Gail Prins for the AR antibody. We are also grateful to LouAnn Hadsell and John Stockton for their excellent technical support. This work was supported by DOD and NIH grants to SY Tsai, an ACS RPG-95-020-04 grant to FJ DeMayo and a DOD fellowship to Z-Q Ma.

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Author notes

  1. Zhi-Qing Ma & Lei Gong

    Present address: Lexicon Genetics, 4000 Research Forest, The Woodlands, 77382, TX

  2. Steven S Chua and Zhi-Qing Ma: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, TX, USA

    Steven S Chua, Francesco J DeMayo & Sophia Y Tsai

  2. Department of Molecular Pathology and Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX77030, Texas, USA

    Lei Gong & Sue-Hwa Lin

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  1. Steven S Chua
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Correspondence to Sophia Y Tsai.

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Chua, S., Ma, ZQ., Gong, L. et al. Ectopic expression of FGF-3 results in abnormal prostate and Wolffian duct development. Oncogene 21, 1899–1908 (2002). https://doi.org/10.1038/sj.onc.1205096

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