T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1

Antonella Bresin, Gianluca Ragone, Cristina Cristofoletti, Diego Arcelli, Cristian Bassi, Elisabetta Caprini, Maria Teresa Fiorenza, Mauro Helmer Citterich, Giandomenico Russo, Maria Grazia Narducci

Research output: Contribution to journalArticle

Abstract

T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when overexpressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/-adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e.The secondary hair germ) and in the stem cell niche (i.e.The bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative-differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/-and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/-mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KCs.

Original languageEnglish
Article numbere0204775
JournalPLoS One
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

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T-Cell Leukemia
T-cells
keratinocytes
somatomedins
Somatomedins
lymphoma
leukemia
Keratinocytes
T-lymphocytes
mice
Hair Follicle
Cell proliferation
Apoptosis
Stem cells
Transgenic Mice
hair follicles
apoptosis
Cell Differentiation
T-Cell Prolymphocytic Leukemia
Keratin-6

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1. / Bresin, Antonella; Ragone, Gianluca; Cristofoletti, Cristina; Arcelli, Diego; Bassi, Cristian; Caprini, Elisabetta; Fiorenza, Maria Teresa; Citterich, Mauro Helmer; Russo, Giandomenico; Narducci, Maria Grazia.

In: PLoS One, Vol. 13, No. 10, e0204775, 01.10.2018.

Research output: Contribution to journalArticle

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AU - Ragone, Gianluca

AU - Cristofoletti, Cristina

AU - Arcelli, Diego

AU - Bassi, Cristian

AU - Caprini, Elisabetta

AU - Fiorenza, Maria Teresa

AU - Citterich, Mauro Helmer

AU - Russo, Giandomenico

AU - Narducci, Maria Grazia

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