Abstract
Benign prostatic hyperplasia (BPH) and prostate cancer are age-related diseases, affecting a majority of elderly men in the western world, and are known to be influenced by several different hormones, including sex hormones. Although the hormone prolactin (PRL) is well known to exert trophic effects on prostate cells, its involvement in pathophysiological conditions is still poorly characterized. In order to evaluate the potential role of PRL in promoting prostate growth, we have used a recently developed transgenic mouse model that overexpresses the PRL gene specifically in the prostate (Pb-PRL transgenic mice). The PRL transgenic mice develop a significant prostate hyperplasia which increases with age. The prostates of the Pb-PRL transgenic mice display a prominent stromal hyperplasia with mild epithelial dysplastic features, leading to an increased stromal/epithelial ratio. Accumulation of secretory material is also a major characteristic. By using cDNA microarray analysis we have obtained interesting insights into the molecular mechanisms involved in the prostate hyperplasia. Of particular interest is the significance of reduced apoptosis for the development/progression of the prostate phenotype. This finding was further confirmed by immunohistochemical analysis using two different apoptosis markers. Moreover, in line with the prominent expansion of the stromal compartment were the identified changes in gene expression seen in the PRL transgenic prostate, suggesting that activation of the stroma is important for the development of the prostate hyperplasia.
Overall, we demonstrate histological and molecular similarities between the prostate hyperplasia of Pb-PRL transgenic mice and human prostate pathology, including both BPH and prostate cancer.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Boyle, P., Maisonneuve, P. & Steg, A. (1996) J Urol 155, 176–80.
Oesterling, J. E. (1996) Prostate Suppl 6, 67–73.
Kyprianou, N., Tu, H. & Jacobs, S. C. (1996) Hum Pathol 27, 668–75.
Claus, S., Berges, R., Senge, T. & Schulze, H. (1997) J Urol 158, 217–21.
Conner, P. & Fried, G. (1998) Acta Obstet Gynecol Scand 77, 249–62.
Doehring, C. B., Sanda, M. G., Partin, A. W., Sauvageot, J., Juo, H., Beaty, T. H., Epstein, J. I., Hill, G. & Walsh, P. C. (1996) Urology 48, 650–3.
Shapiro, E., Becich, M. J., Hartanto, V. & Lepor, H. (1992) J Urol 147, 1293–7.
Robert, M., Costa, P., Bressolle, F., Mottet, N. & Navratil, H. (1995) Br J Urol 75, 317–24.
Deering, R. E., Bigler, S. A., King, J., Choongkittaworn, M., Aramburu, E. & Brawer, M. K. (1994) Urology 44, 64–70.
McNeal, J. E. (1978) Invest Urol 15, 340–5.
Bosch, R. J. (1991) Eur Urol 20, 27–30.
Reiter, E., Hennuy, B., Bruyninx, M., Cornet, A., Klug, M., McNamara, M., Closset, J. & Hennen, G. (1999) Prostate 38, 159–65.
Costello, L. C. & Franklin, R. B. (1994) Prostate 24, 162–6.
Nevalainen, M. T., Valve, E. M., Ingleton, P. M. & Harkonen, P. L. (1996) Endocrinology 137, 3078–88.
Nevalainen, M. T., Valve, E. M., Ingleton, P. M., Nurmi, M., Martikainen, P. M. & Harkonen, P. L. (1997) J Clin Invest 99, 618–27.
Nevalainen, M. T., Valve, E. M., Ahonen, T., Yagi, A., Paranko, J. & Harkonen, P. L. (1997) FASEB J 11, 1297–307.
Ron, M., Fich, A., Shapiro, A., Caine, M. & Ben-David, M. (1981) Urology 17, 235–7.
Negro-Vilar, A., Saad, W. A. & McCann, S. M. (1977) Endocrinology 100, 729–37.
Schacht, M. J., Niederberger, C. S., Garnett, J. E., Sensibar, J. A., Lee, C. & Grayhack, J. T. (1992) Prostate 20, 51–8.
Mori, T. & Nagasawa, H. (1984) Acta Anat (Basel) 120, 180–4.
de Launoit, Y., Kiss, R., Jossa, V., Coibion, M., Paridaens, R. J., De Backer, E., Danguy, A. J. & Pasteels, J. L. (1988) Prostate 13, 143–53.
Janssen, T., Kiss, R. & Schulman, C. (1995) Acta Urol Belg 63, 7–14.
Janssen, T., Darro, F., Petein, M., Raviv, G., Pasteels, J. L., Kiss, R. & Schulman, C. C. (1996) Cancer 77, 144–9.
Ahonen, T. J., Harkonen, P. L., Laine, J., Rui, H., Martikainen, P. M. & Nevalainen, M. T. (1999) Endocrinology 140, 5412–21.
Assimos, D., Smith, C., Lee, C. & Grayhack, J. T. (1984) Prostate 5, 589–95.
Wennbo, H., Kindblom, J., Isaksson, O. G. & Tornell, J. (1997) Endocrinology 138, 4410–5.
Kindblom, J., Dillner, K., Ling, C., Tornell, J. & Wennbo, H. (2002) Prostate 53, 24–33.
Kindblom, J., Dillner, K., Sahlin, L., Robertson, F., Ormandy, C., Tornell, J. & Wennbo, H. (2003) Endocrinology 144, 2269–78.
Park, J. H., Walls, J. E., Galvez, J. J., Kim, M., Abate-Shen, C., Shen, M. M. & Cardiff, R. D. (2002) Am J Pathol 161, 727–35.
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., Gocayne, J. D., Amanatides, P., Ballew, R. M., Huson, D. H., Wortman, J. R., Zhang, Q., Kodira, C. D., Zheng, X. H., Chen, L., Skupski, M., Subramanian, G., Thomas, P. D., Zhang, J., Gabor Miklos, G. L., Nelson, C., Broder, S., Clark, A. G., Nadeau, J., McKusick, V. A., Zinder, N., Levine, A. J., Roberts, R. J., Simon, M., Slayman, C., Hunkapiller, M., Bolanos, R., Delcher, A., Dew, I., Fasulo, D., Flanigan, M., Florea, L., Halpern, A., Hannenhalli, S., Kravitz, S., Levy, S., Mobarry, C., Reinert, K., Remington, K., Abu-Threideh, J., Beasley, E., Biddick, K., Bonazzi, V., Brandon, R., Cargill, M., Chandramouliswaran, I., Charlab, R., Chaturvedi, K., Deng, Z., Di Francesco, V., Dunn, P., Eilbeck, K., Evangelista, C., Gabrielian, A. E., Gan, W., Ge, W., Gong, F., Gu, Z., Guan, P., Heiman, T. J., Higgins, M. E., Ji, R. R., Ke, Z., Ketchum, K. A., Lai, Z., Lei, Y., Li, Z., Li, J., Liang, Y., Lin, X., Lu, F., Merkulov, G. V., Milshina, N., Moore, H. M., Naik, A. K., Narayan, V. A., Neelam, B., Nusskern, D., Rusch, D. B., Salzberg, S., Shao, W., Shue, B., Sun, J., Wang, Z., Wang, A., Wang, X., Wang, J., Wei, M., Wides, R., Xiao, C., Yan, C., Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigó R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X. 1304–51. (2001) Science 291,
Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., Agarwal, P., Agarwala, R., Ainscough, R., Alexandersson, M., An, P., Antonarakis, S. E., Attwood, J., Baertsch, R., Bailey, J., Barlow, K., Beck, S., Berry, E., Birren, B., Bloom, T., Bork, P., Botcherby, M., Bray, N., Brent, M. R., Brown, D. G., Brown, S. D., Bult, C., Burton, J., Butler, J., Campbell, R. D., Carninci, P., Cawley, S., Chiaromonte, F., Chinwalla, A. T., Church, D. M., Clamp, M., Clee, C., Collins, F. S., Cook, L. L., Copley, R. R., Coulson, A., Couronne, O., Cuff, J., Curwen, V., Cutts, T., Daly, M., David, R., Davies, J., Delehaunty, K. D., Deri, J., Dermitzakis, E. T., Dewey, C., Dickens, N. J., Diekhans, M., Dodge, S., Dubchak, I., Dunn, D. M., Eddy, S. R., Elnitski, L., Emes, R. D., Eswara, P., Eyras, E., Felsenfeld, A., Fewell, G. A., Flicek, P., Foley, K., Frankel, W. N., Fulton, L. A., Fulton, R. S., Furey, T. S., Gage, D., Gibbs, R. A., Glusman, G., Gnerre, S., Goldman, N., Goodstadt, L., Grafham, D., Graves, T. A., Green, E. D., Gregory, S., Guigo, R., Guyer, M., Hardison, R. C., Haussler, D., Hayashizaki, Y., Hillier, L. W., Hinrichs, A., Hlavina, W., Holzer, T., Hsu, F., Hua, A., Hubbard, T., Hunt, A., Jackson, I., Jaffe, D. B., Johnson, L. S., Jones, M., Jones, T. A., Joy, A., Kamal, M., Karlsson, E. K., Karolchik D, Kasprzyk A, Kawai J, Keibler E, Kells C, Kent WJ, Kirby A, Kolbe DL, Korf I, Kucherlapati RS, Kulbokas EJ, Kulp D, Landers T, Leger JP, Leonard S, Letunic I, Levine R, Li J, Li M, Lloyd C, Lucas S, Ma B, Maglott DR, Mardis ER, Matthews L, Mauceli E, Mayer JH, McCarthy M, McCombie WR, McLaren S, McLay K, McPherson JD, Meldrim J, Meredith B, Mesirov JP, Miller W, Miner TL, Mongin E, Montgomery KT, Morgan M, Mott R, Mullikin JC, Muzny DM, Nash WE, Nelson JO, Nhan MN, Nicol R, Ning Z, Nusbaum C, O’Connor MJ, Okazaki Y, Oliver K, Overton-Larty E, Pachter L, Parra G, Pepin KH, Peterson J, Pevzner P, Plumb R, Pohl CS, Poliakov A, Ponce TC, Ponting CP, Potter S, Quail M, Reymond A, Roe BA, Roskin KM, Rubin EM, Rust AG, Santos R, Sapojnikov V, Schultz B, Schultz J, Schwartz MS, Schwartz S, Scott C, Seaman S, Searle S, Sharpe T, Sheridan A, Shownkeen R, Sims S, Singer JB, Slater G, Smit A, Smith DR, Spencer B, Stabenau A, Stange-Thomann N, Sugnet C, Suyama M, Tesler G, Thompson J, Torrents D, Trevaskis E, Tromp J, Ucla C, Ureta-Vidal A, Vinson JP, Von Niederhausern AC, Wade CM, Wall M, Weber RJ, Weiss RB, Wendl MC, West AP, Wetterstrand K, Wheeler R, Whelan S, Wierzbowski J, Willey D, Williams S, Wilson RK, Winter E, Worley KC, Wyman D, Yang S, Yang SP, Zdobnov EM, Zody MC, Lander ES. (2002) Nature 420, 520–62.
Dillner, K., Kindblom, J., Flores-Morales, A., Shao, R., Tornell, J., Norstedt, G. & Wennbo, H. (2003) Endocrinology 144, 4955–66.
Tusher, V. G., Tibshirani, R. & Chu, G. (2001) Proc Natl Acad Sci U S A 98, 5116–21.
Stoker, T. E., Robinette, C. L., Britt, B. H., Laws, S. C. & Cooper, R. L. (1999) Biol Reprod 61, 1636–43.
Stoker, T. E., Robinette, C. L. & Cooper, R. L. (1999) Toxicol Sci 52, 68–79.
Dillner, K., Kindblom, J., Flores-Morales, A., Pang, S. T., Tornell, J., Wennbo, H. & Norstedt, G. (2002) Prostate 52, 139–49.
Hsu, S. Y., Kaipia, A., McGee, E., Lomeli, M. & Hsueh, A. J. (1997) Proc Natl Acad Sci U S A 94, 12401–6.
Bruyninx, M., Hennuy, B., Cornet, A., Houssa, P., Daukandt, M., Reiter, E., Poncin, J., Closset, J. & Hennen, G. (1999) Endocrinology 140, 4789–99.
Melkonyan, H. S., Chang, W. C., Shapiro, J. P., Mahadevappa, M., Fitzpatrick, P. A., Kiefer, M. C., Tomei, L. D. & Umansky, S. R. (1997) Proc Natl Acad Sci U S A 94, 13636–41.
Ouyang, X. S., Wang, X., Lee, D. T., Tsao, S. W. & Wong, Y. C. (2001) Carcinogenesis 22, 965–73.
Miyake, H., Nelson, C., Rennie, P. S. & Gleave, M. E. (2000) Cancer Res 60, 170–6.
Thompson, T. C. & Yang, G. (2000) Prostate Suppl 9, 25–8.
Xia, S. J., Xu, C. X., Tang, X. D., Wang, W. Z. & Du, D. L. (2001) Asian J Androl 3, 131–4.
Cardillo, M., Berchem, G., Tarkington, M. A., Krajewski, S., Krajewski, M., Reed, J. C., Tehan, T., Ortega, L., Lage, J. & Gelmann, E. P. (1997) J Urol 158, 212–6.
Kolbusz, W. E., Lee, C. & Grayhack, J. T. (1982) J Urol 127, 581–4.
Ahonen, T. J., Xie, J., LeBaron, M. J., Zhu, J., Nurmi, M., Alanen, K., Rui, H. & Nevalainen, M. T. (2003) J Biol Chem 278, 27287–92.
Li, H., Ahonen, T. J., Alanen, K., Xie, J., LeBaron, M. J., Pretlow, T. G., Ealley, E. L., Zhang, Y., Nurmi, M., Singh, B., Martikainen, P. M. & Nevalainen, M. T. (2004) Cancer Res 64, 4774–82.
Li, H., Zhang, Y., Glass, A., Zellweger, T., Gehan, E., Bubendorf, L., Gelmann, E. P. & Nevalainen, M. T. (2005) Clin Cancer Res 11, 5863–8.
Van Coppenolle, F., Slomianny, C., Carpentier, F., Le Bourhis, X., Ahidouch, A., Croix, D., Legrand, G., Dewailly, E., Fournier, S., Cousse, H., Authie, D., Raynaud, J. P., Beauvillain, J. C., Dupouy, J. P. & Prevarskaya, N. (2001) Am J Physiol Endocrinol Metab 280, E120–9.
Ruffion, A., Al-Sakkaf, K. A., Brown, B. L., Eaton, C. L., Hamdy, F. C. & Dobson, P. R. (2003) Eur Urol 43, 301–8.
Munshi, A., Pappas, G., Honda, T., McDonnell, T. J., Younes, A., Li, Y. & Meyn, R. E. (2001) Oncogene 20, 3757–65.
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y. & Greenberg, M. E. (1997) Cell 91, 231–41.
del Peso, L., Gonzalez-Garcia, M., Page, C., Herrera, R. & Nunez, G. (1997) Science 278, 687–9.
Tessier, C., Prigent-Tessier, A., Ferguson-Gottschall, S., Gu, Y. & Gibori, G. (2001) Endocrinology 142, 4086–94.
Reyes, I., Reyes, N., Iatropoulos, M., Mittelman, A. & Geliebter, J. (2005) Prostate 63, 169–86.
Liotta, L. A. & Kohn, E. C. (2001) Nature 411, 375–9.
Mauch, C., Krieg, T. & Bauer, E. A. (1994) Arch Dermatol Res 287, 107–14.
Hayward, S. W., Rosen, M. A. & Cunha, G. R. (1997) Br J Urol 79 Suppl 2, 18–26.
Tuxhorn, J. A., Ayala, G. E. & Rowley, D. R. (2001) J Urol 166, 2472–83.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press
About this chapter
Cite this chapter
Dillner, K., Kindblom, J., Flores-Morales, A., Wennbo, H. (2008). Gene Expression Studies of Prostate Hyperplasia in Prolactin Transgenic Mice. In: Handwerger, S., Aronow, B. (eds) Genomics in Endocrinology. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-309-7_15
Download citation
DOI: https://doi.org/10.1007/978-1-59745-309-7_15
Publisher Name: Humana Press
Print ISBN: 978-1-58829-651-1
Online ISBN: 978-1-59745-309-7
eBook Packages: MedicineMedicine (R0)