A dominant-negative pleiotrophin mutant introduced by homologous recombination leads to germ-cell apoptosis in male mice

Zhang, Nan; Yeh, Hsiu-Jeng; Zhong, Rong; Li, Yuesheng; Deuel, Thomas F.

doi:10.1073/pnas.96.12.6734

Cited by 32 publications

(22 citation statements)

References 28 publications

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“…Therefore, it might not be surprising that the functional ablation of PTN (Zhang et al, 1999), KGF (Guo et al, 1993) or GM-CSF (Stanley et al, 1994;Dranoff et al, 1994) in mice does not result in an aberrant skin phenotype; SDF-1-deficient animals die as embryos from unrelated defects of the haematopoietic and nervous systems (Ma et al, 1998). Interestingly, expression of all four cytokines in fibroblasts is positively controlled by the proto-oncogene JUN.…”

Section: Discussionmentioning

confidence: 99%

Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts

Florin

Maas‐Szabowski

Werner

et al. 2005

Journal of Cell Science

107

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In skin, fibroblasts of the connective tissue play a decisive role in epidermal homeostasis and repair by contributing to the regulation of keratinocyte proliferation and differentiation. The AP-1 transcription factor subunit JUN plays a crucial role in this mesenchymal-epithelial interplay by regulating the expression of two critical paracrine-acting cytokines, keratinocyte growth factor (KGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). We have performed gene expression profiling of wild-type and Jun–/– mouse embryonic fibroblasts to identify additional players involved in this complex network, and have found pleiotrophin (PTN) and the stromal cell-derived factor 1 (SDF-1) as novel JUN-regulated factors. Both cytokines are expressed by dermal fibroblasts in vivo, as shown by semi-quantitative RT-PCR and in situ hybridization on murine skin sections. Using a heterologous feeder layer co-culture system, we demonstrated that PTN and SDF-1 exert a mitogenic effect on primary human keratinocytes. Moreover, SDF-1-induced keratinocyte proliferation could be specifically inhibited by neutralizing antibodies against SDF-1 or its receptor, CXCR4. Consistent with its role in promoting keratinocyte growth, PTN was upregulated during cutaneous wound healing in vivo. Interestingly, co-cultivation with keratinocytes stimulated PTN expression but repressed SDF-1 production in fibroblasts, demonstrating the complexity of the paracrine regulatory cytokine networks that control skin homeostasis and regeneration.

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Section: Discussionmentioning

confidence: 99%

Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts

Florin

Maas‐Szabowski

Werner

et al. 2005

Journal of Cell Science

107

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“…Pleiotrophin has been implicated in the malignant phenotype of breast and pancreatic cancer (35)(36)(37). Additionally, the v-myc oncogene (P = 0.034) and the mycassociated zinc factor (P = 0.006) were increased in Huvos I/II samples by fold increases of 2.43 and 1.82, respectively.…”

Section: Discussionmentioning

confidence: 99%

An Expression Signature Classifies Chemotherapy-Resistant Pediatric Osteosarcoma

et al. 2005

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“…It seems particularly involved in tumor growth and angiogenesis (9 -11). HARP could also play a central role in normal spermatogenesis, because knock out of the gene in mice may lead to sterility in males (12).…”

mentioning

confidence: 99%

The Lysine-rich C-terminal Tail of Heparin Affin Regulatory Peptide Is Required for Mitogenic and Tumor Formation Activities

Bernard‐Pierrot

Delbé

Caruelle

et al. 2001

Journal of Biological Chemistry

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Heparin affin regulatory peptide (HARP) is a 18-kDa heparin-binding polypeptide that is highly expressed in developing tissues and in several primary human tumors. It seems to play a key role in cellular growth and differentiation. In vitro, HARP displays mitogenic, angiogenic, and neurite outgrowth activities. It is a secreted protein that is organized in two ␤-sheet domains, each domain containing a cluster of basic residues. To assess determinants involved in the biological activities of HARP, C-terminally truncated proteins were produced in Chinese hamster ovary-K1 cells and tested for their mitogenic, tumor formation in nude mice and neurite outgrowth activities. Our data clearly indicate that the residues 111-136 of the lysine-rich C-terminal domain are involved in the mitogenic and tumor formation activities of HARP. Correlatively, no signal transduction was detected using the corresponding mutant, suggesting the absence of HARP binding to its high affinity receptor. However, this C-terminal domain of HARP is not involved in the neurite outgrowth activity. We also demonstrate that HARP signal peptide cleavage could led to two maturated forms that are both but differentially mitogenic.

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A dominant-negative pleiotrophin mutant introduced by homologous recombination leads to germ-cell apoptosis in male mice

Cited by 32 publications

References 28 publications

Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts

Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts

An Expression Signature Classifies Chemotherapy-Resistant Pediatric Osteosarcoma

The Lysine-rich C-terminal Tail of Heparin Affin Regulatory Peptide Is Required for Mitogenic and Tumor Formation Activities

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