Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Differential expression and regulation of the retinoblastoma family of proteins during testicular development and spermatogenesis: roles in the control of germ cell proliferation, differentiation and apoptosis

Oncogene volume 20, pages 1343–1356 (2001)Cite this article

Abstract

Normal spermatogenesis is highly dependent on well-balanced germ cell proliferation, differentiation, and apoptosis. However, the molecular mechanisms that govern these processes are largely unknown. Retinoblastoma family proteins (pRb, p107 and p130) are potentially important regulators of cell growth, differentiation and apoptosis. pRb has been shown to be expressed in the rat testis and involved in the regulation of spermatogenesis. In the present study, the expression and localization of the other two pRb family members, p107 and p130, were analysed at both mRNA and protein levels during testicular development and spermatogenesis using Northern, Western blotting, immunohistochemistry, and in situ hybridization. Furthermore, changes of levels and phosphorylation status of pRb family proteins in response to growth suppression and/or apoptosis induction were investigated using a seminiferous tubule culture system and three animal models. Our data suggest that: (1) pRb family proteins are differentially expressed in the rat testis and they function in a cell-type-specific manner during testicular development and spermatogenesis; (2) they participate in the control of germ cell cycle and act in a cell cycle-phase-specific fashion during germ cell proliferation, and (3) they are also involved in the regulation of apoptosis of germ cells and Leydig cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  • Beumer TL, Kiyokawa H, Roepers-Gajadien HL, van den Bos LA, Lock TM, Gademan IS, Rutgers D, Koff A, de Rooij DG . 1999 Endocrinology 140: 1834–1840

  • Blume-Jensen P, Jiang G, Hyman R, Lee KF, O'Gorman S, Hunter T . 2000 Nat. Genet. 24: 157–162

  • de Rooij DG, Grootegoed JA . 1998 Curr. Opin. Cell Biol. 10: 694–701

  • Dyson N . 1998 Genes Dev. 12: 2245–2262

  • Feng LX, Ravindranath N, Dym M . 2000 J. Biol. Chem. 275: 25572–25576

  • Friend SH, Horowitz JM, Gerber MR, Wang XF, Bogenmann E, Li FP, Weinberg RA . 1987 Proc. Natl. Acad. Sci. USA 84: 9059–9063

  • Gao M, Ossowski L, Ferrari AC . 1999 J. Cell. Physiol. 179: 336–346

  • Garriga J, Limon A, Mayol X, Rane SG, Albrecht JH, Reddy EP, Andres V, Grana X . 1998 Biochem. J. 333: 645–654

  • Grana X, Garriga J, Mayol X . 1998 Oncogene 17: 3365–3383

  • Hakovirta H, Yan W, Kaleva M, Zhang F, Vanttinen K, Morris PL, Soder M, Parvinen M, Toppari J . 1999 Endocrinology 140: 1492–1498

  • Harbour JW, Dean DC . 2000 Nat. Cell. Biol. 2: E65–E67

  • Hardy MP, Zirkin BR, Ewing LL . 1989 Endocrinology 124: 762–770

  • Henriksen K, Hakovirta H, Parvinen M . 1995 Endocrinology 136: 3285–3291

  • Huppi K, Siwarski D, Mock BA, Dosik J, Hamel PA . 1996 Mamm. Genome 7: 353–355

  • Jackson CM, Jackson H . 1984 J. Reprod. Fertil. 71: 393–401

  • Kaelin Jr WG . 1999 Bioessays 21: 950–958

  • Kasten MM, Giordano A . 1998 Cell Death Differ. 5: 132–140

  • Kissel H, Timokhina I, Hardy MP, Rothschild G, Tajima Y, Soares V, Angeles M, Whitlow SR, Manova K, Besmer P . 2000 EMBO J. 19: 1312–1326

  • Krishnamurthy H, Weinbauer GF, Aslam H, Yeung CH, Nieschlag E . 1998 J. Androl. 19: 710–717

  • LeCouter JE, Kablar B, Hardy WR, Ying C, Megeney LA, May LL, Rudnicki MA . 1998a Mol. Cell. Biol. 18: 7455–7465

  • LeCouter JE, Kablar B, Whyte PF, Ying C, Rudnicki MA . 1998b Development 125: 4669–4679

  • LeCouter JE, Whyte PF, Rudnicki MA . 1996 Oncogene 12: 1433–1440

  • Lu J, Danielsen M . 1998 J. Biol. Chem. 273: 31528–31533

  • Lundberg AS, Weinberg RA . 1999 Eur. J. Cancer 35: 1886–1894

  • Mayol X, Garriga J, Grana X . 1995 Oncogene 11: 801–808

  • Mayol X, Grana X, Baldi A, Sang N, Hu Q, Giordano A . 1993 Oncogene 8: 2561–2566

  • McKinnell C, Sharpe RM . 1997 Int. J. Androl. 20: 171–179

  • Mulligan G, Jacks T . 1998 Trends Genet. 14: 223–229

  • Nevins JR . 1998 Cell Growth Differ. 9: 585–593

  • Parvinen M, Vihko KK, Toppari J . 1986 Int. Rev. Cytol. 104: 115–151

  • Pertile P, Baldi A, De Luca A, Bagella L, Virgilio L, Pisano MM, Giordano A . 1995 Cell Growth Differ. 6: 1659–1664

  • Shih HH, Tevosian SG, Yee AS . 1998 Mol. Cell. Biol. 18: 4732–4743

  • Stiegler P, Kasten M, Giordano A . 1998 J. Cell. Biochem. Suppl. 31: 30–36

  • Suter L, Meier G, Bechter R, Bobadilla M . 1998 Arch. Toxicol. 72: 791–797

  • Tajima Y, Sawada K, Morimoto T, Nishimune Y . 1994 J. Reprod. Fertil. 102: 117–122

  • Teerds KJ . 1996 The Leydig cell. Payne AH, Hardy MP and Russell LD (ed). Cache River Press: Vienna, IL, USA pp. 203–219

    Google Scholar 

  • Tena-Sempere M, Zhang FP, Huhtaniemi I . 1994 Endocrinology 135: 1018–1024

  • Tevosian SG, Shih HH, Mendelson KG, Sheppard KA, Paulson KE, Yee AS . 1997 Genes Dev. 11: 383–396

  • Vincent S, Segretain D, Nishikawa S, Nishikawa SI, Sage J, Cuzin F, Rassoulzadegan M . 1998 Development 125: 4585–4593

  • Yan W, Linderborg J, Suominen J, Toppari J . 1999 Endocrinology 140: 1499–1504

  • Yan W, Samson M, Jegou B, Toppari J . 2000a Mol. Endocrinol. 14: 682–699

  • Yan W, Suominen J, Samson M, Jegou B, Toppari J . 2000b Mol. Cell. Endocrinol. 165: 115–129

  • Yan W, Suominen J, Toppari J . 2000c J. Cell Sci. 113: 161–168

  • Yan W, Kero J, Suominen J, Huhtaniemi I, Toppari J . 2000d Dev. Biol. 227: 169–182

  • Yan W, West A, Toppari J, Lahdetie J . 1997 Mol. Cell. Endocrinol. 132: 137–148

  • Yee AS, Shih HH, Tevosian SG . 1998 Front. Biosci. 3: D532–D547

  • Yeh S, Miyamoto H, Nishimura K, Kang H, Ludlow J, Hsiao P, Wang C, Su C, Chang C . 1998 Biochem. Biophys. Res. Commun. 248: 361–367

  • Yoshinaga K, Nishikawa S, Ogawa M, Hayashi S, Kunisada T, Fujimoto T . 1991 Development 113: 689–699

Download references

Acknowledgements

We would like to thank Drs Rene Bernards (The MGH Cancer Center, USA), Michael A Rudnicki (McMaster University, Hamilton, Ontario, Canada), and Loren J Field (Indiana University School of Medicine, Indiana, USA), for providing pRb, p107 and p130 cDNA plasmids respectively. Johanna Vesa is acknowledged for excellent technical assistance. This work was supported by the Academy of Finland, Turku University Central Hospital, and EU contract.

Author information

Authors and Affiliations

  1. Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku, 20520, Finland

    Wei Yan, Jukka Kero, Janne Suominen & Jorma Toppari

  2. Department of Pediatrics, University of Turku, Kiinamyllynkatu 10, Turku, 20520, Finland

    Wei Yan, Jukka Kero & Jorma Toppari

Authors
  1. Wei Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jukka Kero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janne Suominen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jorma Toppari
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yan, W., Kero, J., Suominen, J. et al. Differential expression and regulation of the retinoblastoma family of proteins during testicular development and spermatogenesis: roles in the control of germ cell proliferation, differentiation and apoptosis. Oncogene 20, 1343–1356 (2001). https://doi.org/10.1038/sj.onc.1204254

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204254

Keywords

This article is cited by

Search

Advanced search

Quick links