Cloning and Characterization of the Promoter Region of the Human Keratinocyte Growth Factor Gene

Finch, Paul W.; Lengel, Carole; Chedid, Marcio

doi:10.1074/jbc.270.19.11230

Cited by 36 publications

(22 citation statements)

References 46 publications

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“…Collectively, these data, in conjunction with ours, suggest that LPS induction of KGF-1 expression is mediated through NF-B. However, the promoter region of the KGF-1 gene has two AP-1 transcription factor binding sites (11) and curcumin inhibition of AP-1 may have occurred as well.…”

Section: Discussionsupporting

confidence: 67%

Induction of Keratinocyte Growth Factor 1 Expression by Lipopolysaccharide Is Regulated by CD-14 and Toll-Like Receptors 2 and 4

Putnins

Sanaie

et al. 2002

Infect Immun

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Periodontal disease is a chronic inflammatory condition that is associated with increased concentrations of gram-negative pathogenic bacteria and epithelial cell proliferation. Regulation of this proliferation is poorly understood but is most likely controlled by locally expressed growth factors. Keratinocyte growth factor 1, an epithelium-specific growth factor, is expressed by gingival fibroblasts, and its expression is regulated in a concentration-dependent manner by lipopolysaccharide. In this study, induction of keratinocyte growth factor 1 protein expression was dependent on gingival fibroblast expression of membrane CD14 (mCD14) and Toll-like receptors 2 and 4. Lipopolysaccharides from Escherichia coli and Porphyromonas gingivalis induced membrane expression of CD14 at 1, 3, and 24 h. Specifically, lipopolysaccharide induced low mCD14 expression gingival fibroblasts to express mCD14 at a level consistent with that of high mCD14 expression cells. Functional studies with specific blocking antibodies for CD14 and Toll-like receptors 2 and 4 implicated all of these molecules in signal transduction. The rapid decrease in cell membrane expression of Toll-like receptors 2 and 4 after treatment with lipopolysaccharide was consistent with receptor internalization, and blocking of either of these receptors completely inhibited keratinocyte growth factor 1 protein expression. The transcription factors AP-1 and NF-B were involved in lipopolysaccharide induction of keratinocyte growth factor 1 mRNA and protein expression. These results suggest that lipopolysaccharide may induce proliferation of periodontal epithelial cells by upregulating keratinocyte growth factor 1 expression via the CD14 and Toll-like receptor signaling pathway.

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Section: Discussionsupporting

confidence: 67%

Induction of Keratinocyte Growth Factor 1 Expression by Lipopolysaccharide Is Regulated by CD-14 and Toll-Like Receptors 2 and 4

Putnins

Sanaie

et al. 2002

Infect Immun

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“…Indeed, estrogen-independent activation of ER by growth factors such as EGF 45 and IGF-1 46 and by the elevation of cAMP 45,46 was already known. Considering that promoter of KGF gene harbors semi-palindromic consensus sequences of the estrogen responsive element, 47 our present study showing coexpression of KGF and ER a in human breast cancer cells provides further evidence of the ER a-dependent regulation of KGF expression.…”

Section: Discussionmentioning

confidence: 60%

Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer

Tamaru

Hishikawa

Ejima

et al. 2004

Laboratory Investigation

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Although estrogen is known to play a crucial role in the pathogenesis of breast cancer, the molecular mechanisms underlying the action of estrogen remain elusive. In the present study, we focused on keratinocyte growth factor (KGF) and its receptor (KGFR) in the pathogenesis of breast cancer, as a growth factor mediating estrogen action, since significant roles of KGF were demonstrated in various steroid hormone-dependent tissues. First, using paraffin-embedded specimens from 42 breast cancer patients, we examined expression patterns of KGF and KGFR by both immunohistochemistry using newly generated antibodies and nonradioactive in situ hybridization with T-T dimerized synthetic oligonucleotide probes. We next compared the results with the expression of estrogen receptor (ER) a and b, proliferative activity and apoptotic frequency (TUNEL staining). Also, the similar approaches were taken to analyze the expression and role of KGF in ERpositive (MCF7, ZR-75-1) and ER-negative (SK-BR-3, MDA-MB-231) human breast cancer cell lines in vitro. In the surgical specimens, KGF was expressed in cancer cells as well as stromal cells in 19/42 cases (45%), while KGFR was found in cancer cells in 24/42 cases (57%). The distribution of protein and mRNA in the analysis of both KGF and KGFR expression generally coincided. Moreover, KGF expression was closely associated with the expression of ER a, and the coexpression of KGF and KGFR significantly correlated with lower TUNEL index, but not with proliferative activity. In accordance with the in vivo findings, KGF expression was detected only in ER a-positive MCF7 and ZR-75-1 cells in vitro. And more importantly, we found the inhibitory effect of KGF upon the induction of apoptosis by anticancer drugs in MCF7 cells. Collectively, our results indicate that ER a may be involved in KGF expression, and that KGF may play antiapoptotic roles, rather than mitogenic, in human breast cancer. Keywords: apoptosis; breast cancer; estrogen receptor; immunohistochemistry; in situ hybridization; keratinocyte growth factor; TUNEL staining Breast cancer is the most frequent malignant tumor of women in the USA and European countries. In Japan, the frequency of breast cancer has rapidly increased during the last decade, and currently approximately 20 000 women develop breast cancer per year. However, our knowledge of the development and progression of breast cancer is still largely limited. The proliferation and differentiation of breast cancer cells are influenced by estrogen, 1-3 which exerts its action through binding to estrogen receptor (ER). Currently, ER is categorized into two subtypes, ER a and b, and both are believed to act as an active transcription factor, which binds to a specific DNA segment such as the estrogen responsive element (ERE) and AP-1 site, to regulate the expression of a variety of genes. 4,5 The majority of human breast cancer cells express both ER a and ER b. 6 While ER a is regarded as an indicator of

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“…In vitro binding studies and mutational analysis revealed the importance of Jun and Fos proteins in the expression of mouse M-CSF in ®broblasts and monocytes (Konicek et al, 1998). AP-1 sites have been found in the promoter region of human and murine KGF and GM-CSF genes (Finch et al, 1995;Wang et al, 1994;Ye et al, 1996;Viebig, Szabowski and Angel, unpublished). The importance of AP-1 for the induction of KGF promoter activity during wound healing and repression by glucocorticoids (Brauchle et al, 1995) has not been analysed in detail.…”

Section: Role Of Ap-1 In Wound Healingmentioning

confidence: 99%

Function and regulation of AP-1 subunits in skin physiology and pathology

2001

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The mouse skin has become the model of choice to study the regulation and function of AP-1 subunits in many physiological and pathological processes in vivo and in vitro. Genetically modi®ed mice, in vitro reconstituted skin equivalents and epidermal cell lines were established, in which AP-1-regulated genetic programs of cell proliferation, di erentiation and tumorigenesis can be analysed. Since the epidermis, as our interface with the environment, is subjected to radiation and injury, signal transduction pathways and critical AP-1 members regulating the mammalian stress response could be identi®ed. Regulated expression of important components of the cytokine network, cell surface receptors and proteases, which orchestrate the process of wound healing has been found to rely on AP-1 activity. Here we review our current knowledge on the function of AP-1 subunits and AP-1 target genes in these fascinating ®elds of skin physiology and pathology. Oncogene (2001) 20, 2413 ± 2423.

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Cloning and Characterization of the Promoter Region of the Human Keratinocyte Growth Factor Gene

Cited by 36 publications

References 46 publications

Induction of Keratinocyte Growth Factor 1 Expression by Lipopolysaccharide Is Regulated by CD-14 and Toll-Like Receptors 2 and 4

Induction of Keratinocyte Growth Factor 1 Expression by Lipopolysaccharide Is Regulated by CD-14 and Toll-Like Receptors 2 and 4

Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer

Function and regulation of AP-1 subunits in skin physiology and pathology

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