Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10185-90.
Androgen-induced proliferative quiescence in prostate cancer cells: the role of AS3 as its mediator.

Geck P, Maffini MV, Szelei J, Sonnenschein C, Soto AM.

Department of Anatomy and Cell Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.

In the prostate gland of adult mammals, most epithelial cells are in a state of proliferative quiescence. Androgens regulate this effect by inducing cell cycle arrest in the G(0)/G(1) phase. Potential mediators of this androgen-induced proliferative shutoff were identified by means of subtracted cDNA libraries. The expression pattern of one of these sequences, AS3, strongly correlated with the expression of the androgen-induced proliferative shutoff both temporally and dosewise. The AS3 gene is located on chromosome 13 q12.3, in close proximity to the BRCA2 gene. The loss of chromosomal regions where AS3 alleles are located correlates with various human cancers, including prostate. The biological effect of AS3 was tested in two stable cell lines, one expressing sense and another expressing antisense AS3 constructs, both under tetracycline regulation. S9 cells were obtained by retroviral infection with virions containing a tetracycline-regulated sense AS3 construct. In these cells, sense AS3 was negatively regulated by tetracycline. Tetracycline withdrawal increased the expression of AS3 mRNA and protein. The expression of tetracycline-regulated AS3 resulted in inhibition of cell proliferation. A4 cells were obtained by retroviral infection with virions containing a tetracycline-regulated antisense AS3 construct. Vector-driven expression of antisense-AS3 blocked the induction of androgen-induced endogenous AS3 mRNA and blocked the inhibitory effect of androgens on cell proliferation. Tetracycline-regulated expression of the empty vector control had no effect on cell proliferation. These experiments strongly suggest that AS3 is a mediator of the androgen-induced proliferative shutoff.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10963680&dopt=Abstract antibiotics, tetracycline




Ann Dermatol Venereol. 1998 Dec;125(12):885-7.
[The resistance of Propionibacterium acnes and Staphylococcus epidermidis to cyclines. The Research and Study Group on Acne]

[Article in French]

Noyon V, Legallou F, Richet H, Dreno B.

Laboratoire de Bacteriologie, Virologie, Immunologie, CHU, Nantes.

BACKGROUND: A rising percentage of tetracycline-resistant Propionibacterium acnes strains has been reported in the English literature. PATIENTS AND METHODS: We studied a population of 16 patients with acne who had been treated with oral tetracyclines during the preceding year. A bacteriological examination of a skin biopsy was obtained in all patients to determine aerobic and anaerobic flora as wells as resistance to tetracycline and minocycline. RESULTS: Staphylococcus epidermidis strains were frequently resistant to tetracycline (87.5%) as well as minocycline (30%). Tetracycline-resistant Propionibacterium acnes were also observed (7%). Inversely, we were unable to evidence any minocycline-resistant Propionibacterium acnes strains. CONCLUSION: These findings emphasize the importance of determining whether therapeutic response is related or not to the presence of resistant strains.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9922860&dopt=Abstract antibiotics, tetracycline




Br J Dermatol. 1993 May;128(5):556-60.
Tetracycline-resistant propionibacteria from acne patients are cross-resistant to doxycycline, but sensitive to minocycline.

Eady EA, Jones CE, Gardner KJ, Taylor JP, Cove JH, Cunliffe WJ.

Department of Microbiology, University of Leeds, U.K.

Antibiotic-resistant propionibacteria are being isolated with increasing frequency from antibiotic-treated acne patients. Minimum inhibitory concentrations (MICs) of three tetracyclines, extensively used in acne therapy, were determined for 46 resistant and 19 sensitive propionibacteria isolates. Sensitive strains were inhibited by < or = 1 microgram/ml of all three tetracyclines. For every resistant strain tested, the MIC of tetracycline exceeded that of doxycycline which, in turn, exceeded that of minocycline. The mean MIC for resistant strains was 20.61 +/- 4.56 micrograms/ml of tetracycline, 9.70 +/- 2.03 micrograms/ml of doxycycline and 1.95 +/- 0.35 micrograms/ml of minocycline. In order to determine whether these strains could be inhibited by concentrations of minocycline achievable in vivo, serum levels of minocycline were determined in acne patients receiving either the recommended dose of 50 mg b.d. (20 males, 14 females), or twice this dose (21 males, 12 females). Serum levels were significantly higher (P < 0.001, Student's t-test) in patients receiving 100 mg b.d. Males on 50 mg b.d. had significantly lower serum levels than females on the same dose (P < 0.05. Student's t-test). For all patients, the mean serum level on high-dose minocycline was 2.46 +/- 0.45 micrograms/ml, compared with 1.38 +/- 0.30 micrograms/ml on the smaller dose. These results indicate that tetracycline-resistant propionibacteria should be considered clinically minocycline sensitive, if patients who harbour such strains are prescribed 100 mg b.d. The recommended dose of minocycline for treating acne, especially in male patients, should be re-assessed.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8504049&dopt=Abstract antibiotics, tetracycline




Exp Cell Res. 1995 May;218(1):144-50.
The function of inducible promoter systems in F9 embryonal carcinoma cells.

Miller K, Rizzino A.

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805, USA.

Embryonal carcinoma (EC) cells represent an important model for studying the regulation of cellular differentiation during embryonic development and tumor formation. The differentiation of EC cells is associated with changes in the expression of a number of cellular genes, some of which have been implicated directly in the regulation of differentiation. To facilitate further studies of the possible roles of cellular gene products during the differentiation of EC cells, we have used transient transfection assays to compare the function of three promoter systems that direct the conditional expression of recombinant gene constructs. One system employs the mouse mammary tumor virus (MMTV) promoter, which is induced by glucocorticoid hormones. The other two systems are based on chimeric transactivator proteins consisting of the bacterial lac repressor or tet repressor, respectively, fused with a viral transactivation domain. The chimeric proteins function in mammalian cells as sequence-specific activators of transcription that are regulated by either lactose analogs or tetracycline. Transient transfections of mouse F9 EC cells and their differentiated cells with an MMTV promoter-reporter gene construct and a second plasmid encoding the rat glucocorticoid receptor resulted in a dramatic induction of reporter gene expression by glucocorticoid hormone of approximately 200-fold. The conditional expression system based on the tetracycline-responsive transactivator exhibited a similar range of reporter gene expression in response to tetracycline. In contrast, the system based on the lac repressor exhibited a much more limited range of conditional reporter gene expression in our studies. These findings and others discussed in this report suggest that the tetracycline-responsive promoter system may be useful for the conditional expression of recombinant gene constructs in F9 EC cells. Furthermore, data are presented indicating that the human beta-actin promoter should be suitable for stable expression of conditional transactivators, such as the tetracycline-responsive transactivator, in F9 cells before and after differentiation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7737354&dopt=Abstract antibiotics, tetracycline




Proc Natl Acad Sci U S A. 1976 May;73(5):1509-12.
Synthesis of an R plasmid protein associated with tetracycline resistance is negatively regulated.

Yang HL, Zubay G, Levy SB.

Synthesis of proteins encoded by the R222 plasmid was observed in a DNA-directed cell-free system and the products were compared to those plasmid proteins synthesized in Escherichia coli minicells. A greater number of plasmid-specified proteins was detected in the in vitro system than in the minicell, suggesting the presence of control factors for plasmid gene expression in the minicell. Synthesis of a newly detected plasmid protein (TET protein) is induced by tetracycline in minicells containing tetracycline-resistant plasmids, including R222, and this induced synthesis correlates with induced host resistance to the drug. This TET protein was synthesized in vitro from R222 DNA in the absence of tetracycline, indicating that no positive regulatory role for tetracycline is required for the protein's synthesis. TET proteon synthesis was inhibited in vitro when cell-free extracts prepared from cells containing the R222 plasmid were used.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=775491&dopt=Abstract antibiotics, tetracycline




Biochem Biophys Res Commun. 1996 Dec 24;229(3):930-7.
A tetracycline-responsive promoter system reveals the role of a secreted binding protein for FGFs during the early phase of tumor growth.

Liaudet-Coopman ED, Schulte AM, Cardillo M, Wellstein A.

Lombardi Cancer Center, Georgetown University, 3970 Reservoir Road, Washington, DC, 20007, USA.

We showed previously that a secreted binding protein for FGFs (BP) can induce tumor growth and angiogenesis of a non-tumorigenic human cell line (SW-13). To study the contribution of BP to different phases of tumor growth, we employed a regulated promoter system which is highly active in SW-13 cells and can be downregulated >20-fold by treatment with tetracycline. We demonstrate that expression of BP in SW-13 cells (SW-13/tetBP cells) induces colony formation in soft agar and tumor growth in athymic nude mice. Tetracycline downregulated BP expression in these cells and prevented their colony formation in soft agar. Continuous tetracycline treatment of animals suppressed BP expression in tumors grown from SW-13/tetBP cells and reduced growth of the xenografts. Initiation of tetracycline treatment after xenograft tumors had been established had no effect on further tumor expansion in spite of downregulated BP levels. These data suggest that BP expression plays a role mainly in the early stages of tumor progression.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8954996&dopt=Abstract antibiotics, tetracycline




Antibiot Khimioter. 1995 Oct;40(10):7-14.
[Chelating and oxidizing properties of tetracycline metabolites forming during its peroxidase or photoinduced oxidation]

[Article in Russian]

Petrenko IuM, Titov VIu, Vladimirov IuA.

Tetracycline metabolites forming on the antibiotic exposure to visible light or peroxidase as well as tetracycline as such showed the ability to bind iron cations. When the metabolites bound the cations of iron protoxide, they catalyzed its oxidation. Chelating agents such as o-phenanthroline and EDTA arrested the ions of iron protoxide and iron oxide in the respective iron/tetracycline complexes at a much lower rate than that with the use of the native tetracycline. This means that the affinity of the metabolites with the above mentioned iron ions was much higher than that of the native tetracycline. When the metabolites and tetracycline bound iron protoxide, they catalyzed its oxidation to the oxide. Tetracycline and its metabolites were shown as well to have the property of reversible regeneration of iron oxide to the protoxide.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8660122&dopt=Abstract antibiotics, tetracycline




Adv Dent Res. 1998 Nov;12(2):152-8.
Tetracyclines inhibit protein glycation in experimental diabetes.

Ryan ME, Ramamurthy NS, Golub LM.

Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York at Stony Brook 11794-8702, USA.

Glycation of proteins, which is accelerated in the diabetic state, has been implicated in many of the long-term complications of diabetes. This process can be inhibited by members of the tetracycline family of compounds. This novel finding is supported by studies conducted on drug (streptozotocin)induced Type I and genetic (ZDF/Gmi-fa/fa) Type II diabetic rats. These animals were orally gavaged daily with 5 mg of doxycycline and a variety of non-antimicrobial chemically modified tetracycline derivatives for time periods of 3 weeks to 11 months, while control untreated diabetic and nondiabetic animals were gavaged with vehicle alone (2% CMC). Blood and tissue samples were collected and analyzed for glucose and glycated proteins. None of the treatments had any effect on the severity of hyperglycemia or the intracellular glycation of hemoglobin of either Type I or II diabetic animals. However, the tetracycline analogues did affect the extracellular glycation of several proteins such as those found in the serum as well as skin collagen. In the Type II (ZDF) animals, initial mortality (3-5 months) was seen only in the doxycycline-treated animals, associated with infection by tetracycline-resistant micro-organisms, which was eventually surpassed by mortality rates in the untreated diabetics (6-9 months). CMT treatment not only decreased mortality but also increased longevity in the Type II diabetic animals, most likely by preventing the development of a number of long-term complications of uncontrolled diabetes, including glycation of proteins, that eventually lead to the demise of untreated diabetic animals.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9972141&dopt=Abstract antibiotics, tetracycline