Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

Hoover, Russell R.; Thomas, Klaus H.; Floros, Joanna

doi:10.1042/bj3400069

Cited by 21 publications

(26 citation statements)

References 36 publications

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“…Whereas no effect of Dex or cAMP was observed on expression of TK:hGH, Dex caused a 50% inhibition of cAMP-induced SP-A Ϫ990 :TK:hGH expression (data not shown), suggesting that Dex inhibition is mediated through SP-A 5Ј-flanking sequences between Ϫ47 and Ϫ990 bp. These findings differ from those of Hoover and colleagues (25), who reported that a region between Ϫ32 and ϩ63 bp of the hSP-A1 gene mediates Dex repression of transcription.…”

Section: Dex Acting Through the Gr Inhibits Sp-contrasting

confidence: 56%

Glucocorticoid inhibition ofSP-Agene expression in lung type II cells is mediated via the TTF-1-binding element

Alcorn¹,

Islam²,

Young³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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In lung cells transfected with a fusion gene containing three TBEs fused to the basal SP-A promoter, Dex prevented the stimulatory effect of IL-1 on TTF-1 induction of SP-A promoter activity, suggesting that the GR inhibits SP-A promoter activity through the TBE. In gel shift assays using nuclear extracts from human fetal type II cells cultured in the absence or presence of cAMP, Dex markedly reduced binding of nuclear proteins to the TBE and blocked the stimulatory effect of cAMP on TBE-binding activity. Our finding that Dex increased expression of the NF-B inhibitory partner IB-␣ suggests that the decrease in TBE-binding activity may be caused, in part, by GR inhibition of NF-B interaction with this site. surfactant protein A; fetal lung; glucocorticoid receptor; cAMP; thyroid transcription factor-1

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Section: Dex Acting Through the Gr Inhibits Sp-contrasting

confidence: 56%

Glucocorticoid inhibition ofSP-Agene expression in lung type II cells is mediated via the TTF-1-binding element

Alcorn¹,

Islam²,

Young³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…A feature of the hSPA promoter that additionally makes it potentially useful in gene therapy is that it has a region that enables glucocorticoid-mediated inhibition of transcription enabling the in vivo control of gene therapy by glucocorticoid drugs. Hoover et al (36) identified the region of the hSPA1 promoter between ϩ14 and ϩ59 that is repressed by glucocorticoid, and this region included two negative glucocorticoid responsive elements (Fig. 3B).…”

Section: Design Of Cancer-targeted Tissue-specific Promoter Systemmentioning

confidence: 99%

Development of a Cancer-Targeted Tissue-Specific Promoter System

et al. 2004

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Present cancer gene therapy using proapoptotic genes has had limited success because the therapy is prone to cause side effects as a result of the lack of tissue and cancer specificity. To target cancer cells without damaging normal cells, we have designed a novel dual promoter system in which a tissue-specific transcription system under the control of a cancerspecific promoter drives expression of a therapeutic gene. The applicability of this system was demonstrated by adapting it to target lung cancer. We termed this lung cancer system TTS (TTF1 gene under the control of human telomerase reverse transcriptase promoter and human surfactant protein A1 promoter). The TTS system showed much higher promoter activity in lung cancer cells compared with other kinds of cancer and normal lung cells, including stem cells. Moreover, insertion of negative glucocorticoid responsive elements in the system allows it to be drug controllable. The approaches that we have used could be adapted to target other types of cancer. We report a novel cancer-targeted tissue-specific dual promoter system designed for gene therapy.

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“…The glucocorticoid effect on human SP-A gene expression is complex because it may involve transcriptional and posttranscriptional events (8,27,28,43,52). In human fetal lung explants, GCs reduce SP-A gene expression in a time-and dose-dependent manner.…”

mentioning

confidence: 99%

“…It was suggested that this biphasic decay rate was a result of differential effects of Dex on SP-A1 and SP-A2 mRNA stabilities. In fact, the two SP-A genes have been shown to be differentially regulated by certain agents, including GCs (27,31,35,42,55), and certain SP-A alleles may be differentially regulated by Dex (26).…”

mentioning

confidence: 99%

Human SP-A 3′-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone

Wang¹,

Guo²,

Floros

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Human surfactant protein A (SP-A) is encoded by two genes ( SP-A1, SP-A2), and each is identified with several alleles. SP-A is involved in normal lung function, innate immunity, inflammatory processes, and is regulated by glucocorticoids. We investigated the role of 3′-untranslated region (UTR) of 10 SP-A variants on gene expression using transient transfection of 3′-UTR constructs in the human lung adenocarcinoma cell line NCI-H441. We found: 1) both basal mRNA and protein levels of the reporter gene of SP-A 3′-UTR constructs are significantly ( P < 0.01) reduced compared with controls (vector pGL3 and surfactant protein B pGL3) and that differences exist among alleles; and 2) after dexamethasone (Dex) treatment (100 nM for 16 h), mRNA was reduced (31–51%). Seven alleles showed a significant decrease ( P < 0.05) in mRNA, and three did not. Reporter activity was also decreased, from 17% (1A1) to 38% (1A), with six alleles showing a significant decrease. The data indicate that the 3′-UTR of SP-As play a differential role in SP-A basal expression and in response to Dex. Therefore, a careful consideration of individual use of steroid treatment may be considered.

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Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

Cited by 21 publications

References 36 publications

Glucocorticoid inhibition ofSP-Agene expression in lung type II cells is mediated via the TTF-1-binding element

Glucocorticoid inhibition ofSP-Agene expression in lung type II cells is mediated via the TTF-1-binding element

Development of a Cancer-Targeted Tissue-Specific Promoter System

Human SP-A 3′-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone

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