A distinct expression pattern of cyclin K in mammalian testes suggests a functional role in spermatogenesis

PLoS One. 2014 Jul 8;9(7):e101539. doi: 10.1371/journal.pone.0101539. eCollection 2014.

Abstract

Germ cell and embryonic stem cells are inextricably linked in many aspects. Remarkably both can generate all somatic cell types in organisms. Yet the molecular regulation accounting for these similarities is not fully understood. Cyclin K was previously thought to associate with CDK9 to regulate gene expression. However, we and others have recently shown that its cognate interacting partners are CDK12 and CDK13 in mammalian cells. We further demonstrated that cyclin K is essential for embryonic stem cell maintenance. In this study, we examined the expression of cyclin K in various murine and human tissues. We found that cyclin K is highly expressed in mammalian testes in a developmentally regulated manner. During neonatal spermatogenesis, cyclin K is highly expressed in gonocytes and spermatogonial stem cells. In adult testes, cyclin K can be detected in spermatogonial stem cells but is absent in differentiating spermatogonia, spermatids and spermatozoa. Interestingly, the strongest expression of cyclin K is detected in primary spermatocytes. In addition, we found that cyclin K is highly expressed in human testicular cancers. Knockdown of cyclin K in a testicular cancer cell line markedly reduces cell proliferation. Collectively, we suggest that cyclin K may be a novel molecular link between germ cell development, cancer development and embryonic stem cell maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Proliferation
  • Cyclins / genetics*
  • Cyclins / metabolism
  • Embryonic Stem Cells / metabolism
  • Gene Expression
  • Gene Expression Regulation, Developmental*
  • Germ Cells / metabolism
  • Humans
  • Male
  • Mammals / genetics
  • Mice
  • Spermatogenesis / genetics*
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / metabolism
  • Testis / metabolism*

Substances

  • CCNK protein, human
  • Cyclins

Grants and funding

Financial support is provided by grants from the National Basic Research Program of China/973 (2011CB504200 and 2012CB910700), the National Natural Science Foundation of China (31171260, 81261120399, 81330054, and J1103518), and the Science and Technology Department of Sichuan Province (2013JQ0041). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.