Lactogenic Hormone and Cell Type-Specific Control of the Whey Acidic Protein Gene Promoter in Transfected Mouse Cells

Doppler, Wolfgang; Villunger, Andreas; Jennewein, Patricia; Brduscha, Karin; Groner, Bernd; Ball, Roland K.

doi:10.1210/mend-5-11-1624

Cited by 67 publications

(47 citation statements)

References 29 publications

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“…The WAP gene is expressed in mammary epithelial cells during late pregnancy and throughout lactation. Its expression is regulated by a variety of l a c t o g e n i c h o r m o n e s , s u c h a s i n s u l i n , glucocorticoid, and prolactin [11][12][13]. WAPs have a signal peptide [14] and two domain structures with a four-disulfide core (4-DSC) in a conserved arrangement [15].…”

mentioning

confidence: 99%

Whey Acidic Protein (WAP) Depresses the Proliferation of Mouse (MMT) and Human (MCF-7) Mammary Tumor Cells

Nukumi

Iwamori

Naito

et al. 2005

Journal of Reproduction and Development

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Abstract. We previously reported that the enforced expression of exogenous whey acidic protein (WAP) significantly inhibited the proliferation of mouse mammary epithelial cells (HC11 and EpH4/ H6 cells). This paper presents the first evidence that WAP also depresses the proliferation of mammary tumor cells from mouse (MMT cells) and human (MCF-7 cells). We established WAPclonal MMT and MCF-7 cell lines, and confirmed the secretion of WAP from the WAP-clonal cells into culture medium. The enforced expression of WAP significantly inhibited the proliferation of MMT and MCF-7 cells in in vitro culture. FACScan analyses revealed that G0/G1 phase cell-cycle progression was disordered and elongated in the WAP-clonal MMT and MCF-7 cells compared to that of the control cells. The expression of cyclin D1 was significantly decreased in the WAP-clonal MMT and MCF-7 cells, suggesting that progression from the G1 to the S phase was delayed in the WAPclonal cells. The present results indicate that WAP plays a negative regulatory role in the cell-cycle progression of mammary tumor cells via a paracrine mechanism.

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mentioning

confidence: 99%

Whey Acidic Protein (WAP) Depresses the Proliferation of Mouse (MMT) and Human (MCF-7) Mammary Tumor Cells

Nukumi

Iwamori

Naito

et al. 2005

Journal of Reproduction and Development

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“…Mobility shift and exonuclease protection assays have determined the presences of binding sites for Stat 5 (involved in the prolactin response), glucocorticoid receptor (GR) complex and other factors necessary for transcription in the proximal promoter region (Watson et al, 1991;Welte et al, 1993;Lubon and Hennighausen, 1987;. Deletional analysis of the promoter in transfected HC11 cells has determined two regions between -2500 to -1500 and -450 to -1 that contain hormone response elements (Doppler et al, 1991). Further deletional analysis of the -219 to -1 segment identified an essential hormone induced enhancer region at -195 and a repressor region between -219 and -195 (Mink et al, 1992).…”

Section: Gene Regulation Of the Murine Whey Acidic Protein Promotermentioning

confidence: 99%

Production and secretion of recombinant human fibrinogen by the transgenic murine mammary gland

Butler¹,

O'Sickey²,

Lord³

et al. 1999

Theriogenology

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The mammary gland of lactating transgenic animals has several advantages for production of heterologous proteins including a high cell density that results in high concentrations of secreted protein and the ability to perform several types of post-translational modifications. Transgenes were constructed from the 4.1 kbp murine Whey Acidic Protein promoter (mWAP) and the three cDNAs coding for the A", B$ and ( fibrinogen chains to evaluate the requirements of the transgenic murine mammary gland for high level secretion of fully assembled human fibrinogen. After introducing the constructs into the murine zygotes by microinjection, secretion of fully assembled fibrinogen into milk was measured at concentrations between 10 :g/ml to 200 :g/ml.In one line of mice the total secretion of fibrinogen and unassembled subunits approached 700 :g/ml in milk. The level of assembled fibrinogen was proportional to the lowest amount of subunit produced where both the B$ and ( chains were rate limiting. Also, the subunit complexes ( 2 , A"( 2 and the individual subunits A", B$ and ( were found as secretion products. This is the first time that secretion of individual B$-subunits by any cell type has been reported and suggests the organization of the secretion pathway in mammary epithelia is different from that in liver. Glycosylated forms of individual B$-chain contained a complex saccharide with low mannose. Glycosylation of the (-chain was also observed. These results suggest the 4.1 mWAP promoter can drive expression of fibrinogen cDNAs to high levels and that the amount of fully assembled fibrinogen secreted is equal to the level of the lowest expressing chain.iii

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“…Quantitation of RNA was performed as described previously (Doppler et al, 1991). Briefly, an aliquot corresponding to 400 ng of RNA was reverse transcribed.…”

Section: Quantitation Of Rnamentioning

confidence: 99%

Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT-5 activation in breast cancer cells in vitro

Widschwendter

Welte

et al. 1998

Br J Cancer

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Summary Two recent papers demonstrate that prolactin plays an important role in the induction and progression of mammary tumours. Retinoids have been shown to be potent inhibitors of breast carcinogenesis. We studied expression of prolactin receptor mRNA in human breast cancer cell lines MCF-7, SKBR-3, T47D and BT-20 treated with and without retinoids using Northern blot and a quantitative polymerase chain reaction (PCR) method. In all cell lines, all-trans-and 9-cis-retinoic acid, as well as the retinoic acid receptor γ (RAR-γ) selective agonists CD2325 and CD437 (1 µM), were able to down-regulate prolactin receptor. After 1 h, a significant reduction was detectable and maximal effect was achieved after 24 h of treatment. Pretreatment with retinoic acid also reduced the prolactin-/prolactin receptordependent signal transduction and activation of transcription 5 (STAT-5) activation in T47D cells. Cycloheximide failed to abrogate the retinoic acid-induced decline in prolactin receptor mRNA levels, indicating that this effect was not dependent upon continuing protein synthesis. Similarly, no change in the stability of prolactin receptor mRNA was observed during 12 h of retinoic acid treatment. In conclusion, our results demonstrate that retinoids are able to inhibit the expression of prolactin receptor message, which encodes an important growth factor receptor in breast cancer cells. This action could be responsible for the anti-tumour effects of retinoids.

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Lactogenic Hormone and Cell Type-Specific Control of the Whey Acidic Protein Gene Promoter in Transfected Mouse Cells

Cited by 67 publications

References 29 publications

Whey Acidic Protein (WAP) Depresses the Proliferation of Mouse (MMT) and Human (MCF-7) Mammary Tumor Cells

Whey Acidic Protein (WAP) Depresses the Proliferation of Mouse (MMT) and Human (MCF-7) Mammary Tumor Cells

Production and secretion of recombinant human fibrinogen by the transgenic murine mammary gland

Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT-5 activation in breast cancer cells in vitro

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