TCL1 participates in early embryonic development and is overexpressed in human seminomas

Overexpression of the TCL1 oncogene has been shown to play a causative role in T cell leukemias of humans and mice. The characterization of Tcl1-deficient mice in these studies indicates an important developmental role for Tcl1 in early embryogenesis. In wild-type embryos, Tcl1 is abundant in the first three mitotic cycles, during which it shuttles between nuclei and the embryo cortical regions in a cell-cycle-dependent fashion. The absence of this protein in early embryogenesis results in reduced fertility of female mice. The present studies elucidate the mechanism responsible for the reduced female fertility through analysis of the oogenesis stages and early embryo development in Tcl1-deficient mice. Even though Tcl1−/− females display normal oogenesis and rates of oocyte maturation/ovulation and fertilization, the lack of maternally derived Tcl1 impairs the embryo's ability to undergo normal cleavage and develop to the morula stage, especially under in vitro culture conditions. Beyond this crisis point, differentiative traits of zygotic genome activation and embryo compaction can take place normally. In contrast with this unanticipated role in early embryogenesis, we observed an overexpression of TCL1 in human seminomas. This finding suggests that TCL1 dysregulation could contribute to the development of this germinal cell cancer as well as lymphoid malignancies.

[1]  M. Stern,et al.  Identification of Akt Association and Oligomerization Domains of the Akt Kinase Coactivator TCL1 , 2002, Molecular and Cellular Biology.

[2]  J. Laine,et al.  Differential Regulation of Akt Kinase Isoforms by the Members of the TCL1 Oncogene Family* , 2002, The Journal of Biological Chemistry.

[3]  I. Roninson,et al.  Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. , 2001, Genes & development.

[4]  J. Laine,et al.  The protooncogene TCL1 is an Akt kinase coactivator. , 2000, Molecular cell.

[5]  C D Baroni,et al.  Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues. , 2000, Cancer research.

[6]  M. Fiorenza,et al.  A developmentally regulated GAGA box-binding factor and Sp1 are required for transcription of the hsp70.1 gene at the onset of mouse zygotic genome activation. , 2000, Development.

[7]  Y. Pekarsky,et al.  Genomic analysis of human and mouse TCL1 loci reveals a complex of tightly clustered genes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. Capco,et al.  Regulation of cell adhesion during embryonic compaction of mammalian embryos: Roles for PKC and β‐catenin , 1999, Molecular reproduction and development.

[9]  C. Denny,et al.  TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Isobe,et al.  Identification of the TCL1/MTCP1-like 1 (TML1) gene from the region next to the TCL1 locus. , 1999, Cancer research.

[11]  Y. Pekarsky,et al.  Abnormalities at 14q32.1 in T cell malignancies involve two oncogenes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  F. Sigaux,et al.  Transgenic mice for MTCP1 develop T-cell prolymphocytic leukemia. , 1998, Blood.

[13]  Masao Seto,et al.  Expression of the TCL1 Gene at 14q32 in B‐Cell Malignancies but Not in Adult T‐Cell Leukemia , 1998, Japanese journal of cancer research : Gann.

[14]  M. Fiorenza,et al.  Quantitative RT-PCR amplification of RNA in single mouse oocytes and preimplantation embryos. , 1998, BioTechniques.

[15]  C. Croce,et al.  Crystal structure of MTCP-1: implications for role of TCL-1 and MTCP-1 in T cell malignancies. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[16]  G. Russo,et al.  Deregulated expression of TCL1 causes T cell leukemia in mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Russo,et al.  TCL1 is overexpressed in patients affected by adult T-cell leukemias. , 1997, Cancer research.

[18]  Antonio Facchiano,et al.  The murine Tcl1 oncogene: embryonic and lymphoid cell expression , 1997, Oncogene.

[19]  S. Butz,et al.  An alpha-E-catenin gene trap mutation defines its function in preimplantation development. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  L. Kinnunen,et al.  Stage-specific regulation of murine Hsp68 gene promoter in preimplantation mouse embryos. , 1995, Developmental biology.

[21]  M. Isobe,et al.  Identification of the TCL1 gene involved in T-cell malignancies. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  F. Sigaux,et al.  MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations. , 1993, Oncogene.

[23]  R. Schultz,et al.  Stage-specific expression of a family of proteins that are major products of zygotic gene activation in the mouse embryo. , 1991, Developmental biology.

[24]  P. Nowell,et al.  Molecular analysis of a t(7;14)(g35;g32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia , 1988, Cell.

[25]  M. Morange,et al.  Heat shock proteins, first major products of zygotic gene activity in mouse embryo , 1983, Nature.

[26]  N. Minami,et al.  Analysis of Gene Expression in Mouse 2-Cell Embryos Using Fluorescein Differential Display: Comparison of Culture Environments1 , 2001, Biology of reproduction.

[27]  J. Renard,et al.  Expression of the HSP 70.1 gene, a landmark of early zygotic activity in the mouse embryo, is restricted to the first burst of transcription. , 1995, Development.