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Transcriptomic signature of bexarotene (rexinoid LGD1069) on mammary gland from three transgenic mouse mammary cancer models.

Abba MC, Hu Y, Levy CC, Gaddis S, Kittrell FS, Zhang Y, Hill J, Bissonnette RP, Medina D, Brown PH, Aldaz CM - BMC Med Genomics (2008)

Bottom Line: The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis.This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries.Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Carcinogenesis, The University of Texas M,D, Anderson Cancer Center, Science Park-Research Division, Smithville, 78957, TX, USA. mabba777@hotmail.com

ABSTRACT

Background: The rexinoid bexarotene (LGD1069, Targretin) is a highly selective retinoid x receptor (RXR) agonist that inhibits the growth of pre-malignant and malignant breast cells. Bexarotene was shown to suppress the development of breast cancer in transgenic mice models without side effects. The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis. Our goal in the present study was to obtain a profile of the genes modulated by bexarotene on mammary gland from three transgenic mouse mammary cancer models in an effort to elucidate its molecular mechanism of action and for the identification of biomarkers of effectiveness.

Methods: Serial analysis of gene expression (SAGE) was employed to profile the transcriptome of p53-, MMTV-ErbB2, and C3(1)-SV40 mammary cells obtained from mice treated with bexarotene and their corresponding controls.

Results: This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries. Analysis of gene expression changes induced by bexarotene in mammary gland revealed that 89 genes were dysregulated among the three transgenic mouse mammary models. From these, 9 genes were common to the three models studied.

Conclusion: Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.

No MeSH data available.


Related in: MedlinePlus

Deregulated transcripts in mammary gland by systemic treatment with bexarotene in the three transgenic mice mammary cancer models.A. Scatter-plot representation of differentially expressed genes between bexarotene treated mice and vehicle control SAGE libraries (p < 0.05). B. Gene ontology (GO) classification of bexarotene induced differentially expressed transcripts on mammary gland from the different transgenic models. Relative representation of the deregulated transcripts with specific GO term annotations related to biological processes or molecular function.
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Figure 2: Deregulated transcripts in mammary gland by systemic treatment with bexarotene in the three transgenic mice mammary cancer models.A. Scatter-plot representation of differentially expressed genes between bexarotene treated mice and vehicle control SAGE libraries (p < 0.05). B. Gene ontology (GO) classification of bexarotene induced differentially expressed transcripts on mammary gland from the different transgenic models. Relative representation of the deregulated transcripts with specific GO term annotations related to biological processes or molecular function.

Mentions: In order to identify rexinoid-regulated biomarkers, we generated six mouse SAGE libraries corresponding to mammary gland samples from control and bexarotene treatment from three transgenic mouse mammary cancer models: p53-Null [10], MMTV-erbB2 [8] and C3(1)/SV40 T-antigen [9]. This resulted in the sequencing of 360,000 tags (60,000 tags per library), thus monitoring the behavior of more than 20,000 transcript tags. Our statistical analyses revealed 236 transcripts differentially regulated by bexarotene treatment in mammary epithelium from p53- background, 283 transcripts in mammary gland from the MMTV-erbB2 model, and 290 transcripts in the C3(1)/SV40 T-antigen transgenic mice mammary model (Figure 2A; see Additional file 1). Table 1 shown the most highly bexarotene deregulated transcripts from each transgenic mice mammary cancer model (Fold change ≥ 7; p < 0.01).


Transcriptomic signature of bexarotene (rexinoid LGD1069) on mammary gland from three transgenic mouse mammary cancer models.

Abba MC, Hu Y, Levy CC, Gaddis S, Kittrell FS, Zhang Y, Hill J, Bissonnette RP, Medina D, Brown PH, Aldaz CM - BMC Med Genomics (2008)

Deregulated transcripts in mammary gland by systemic treatment with bexarotene in the three transgenic mice mammary cancer models.A. Scatter-plot representation of differentially expressed genes between bexarotene treated mice and vehicle control SAGE libraries (p < 0.05). B. Gene ontology (GO) classification of bexarotene induced differentially expressed transcripts on mammary gland from the different transgenic models. Relative representation of the deregulated transcripts with specific GO term annotations related to biological processes or molecular function.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2563021&req=5

Figure 2: Deregulated transcripts in mammary gland by systemic treatment with bexarotene in the three transgenic mice mammary cancer models.A. Scatter-plot representation of differentially expressed genes between bexarotene treated mice and vehicle control SAGE libraries (p < 0.05). B. Gene ontology (GO) classification of bexarotene induced differentially expressed transcripts on mammary gland from the different transgenic models. Relative representation of the deregulated transcripts with specific GO term annotations related to biological processes or molecular function.
Mentions: In order to identify rexinoid-regulated biomarkers, we generated six mouse SAGE libraries corresponding to mammary gland samples from control and bexarotene treatment from three transgenic mouse mammary cancer models: p53-Null [10], MMTV-erbB2 [8] and C3(1)/SV40 T-antigen [9]. This resulted in the sequencing of 360,000 tags (60,000 tags per library), thus monitoring the behavior of more than 20,000 transcript tags. Our statistical analyses revealed 236 transcripts differentially regulated by bexarotene treatment in mammary epithelium from p53- background, 283 transcripts in mammary gland from the MMTV-erbB2 model, and 290 transcripts in the C3(1)/SV40 T-antigen transgenic mice mammary model (Figure 2A; see Additional file 1). Table 1 shown the most highly bexarotene deregulated transcripts from each transgenic mice mammary cancer model (Fold change ≥ 7; p < 0.01).

Bottom Line: The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis.This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries.Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Carcinogenesis, The University of Texas M,D, Anderson Cancer Center, Science Park-Research Division, Smithville, 78957, TX, USA. mabba777@hotmail.com

ABSTRACT

Background: The rexinoid bexarotene (LGD1069, Targretin) is a highly selective retinoid x receptor (RXR) agonist that inhibits the growth of pre-malignant and malignant breast cells. Bexarotene was shown to suppress the development of breast cancer in transgenic mice models without side effects. The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis. Our goal in the present study was to obtain a profile of the genes modulated by bexarotene on mammary gland from three transgenic mouse mammary cancer models in an effort to elucidate its molecular mechanism of action and for the identification of biomarkers of effectiveness.

Methods: Serial analysis of gene expression (SAGE) was employed to profile the transcriptome of p53-, MMTV-ErbB2, and C3(1)-SV40 mammary cells obtained from mice treated with bexarotene and their corresponding controls.

Results: This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries. Analysis of gene expression changes induced by bexarotene in mammary gland revealed that 89 genes were dysregulated among the three transgenic mouse mammary models. From these, 9 genes were common to the three models studied.

Conclusion: Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.

No MeSH data available.


Related in: MedlinePlus