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Progesterone regulates the proliferation of breast cancer cells - in vitro evidence.

Azeez JM, Sithul H, Hariharan I, Sreekumar S, Prabhakar J, Sreeja S, Pillai MR - Drug Des Devel Ther (2015)

Bottom Line: Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome.Therefore, we further functionally characterized the protein product of TOB-1 in vitro.These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.

ABSTRACT
Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome. From previous studies, we identified differentially expressed genes in each menstrual cycle phase by microarray, then subjected them to functional in vitro analyses. Microarray studies disclosed genes that are upregulated in the luteal phase and follicular phase. TOB-1 is a tumor suppressor gene and was expressed exclusively in the luteal phase in our microarray study. Therefore, we further functionally characterized the protein product of TOB-1 in vitro. To our knowledge, no studies have yet been conducted on reactive oxygen species-regulated tumor suppressor interactions in accordance with the biphasic nature of progesterone. This work demonstrates that progesterone can produce reactive oxygen species in MCF-7 cells and that TOB-1 exerts a series of non-genomic interactions that regulate antiproliferative activity by modulating the antioxidant enzyme superoxide dismutase. Furthermore, this study implicates PTEN as an interacting partner for TOB-1, which may regulate the downstream expression of cell cycle control protein p27 via multiple downstream signaling pathways of progesterone through a progesterone receptor, purely in a time- and concentration-dependent manner. These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival.

No MeSH data available.


Related in: MedlinePlus

Progesterone induces mild chromatin condensation and apoptosis.Notes: MCF-7 cells induced by progesterone for 24, 48, and 72 hours were stained with (A) Hoechst 33342 nuclear staining for chromatin condensation and viewed under an Eclipse E-600 fluorescence microscope (×400). (B) Annexin V-FITC/PI double-stained cells were used to assess apoptosis/necrosis by flow cytometry. Cells in the lower right quadrant indicate Annexin-positive/PI-negative, early apoptotic cells. The cells in the upper right quadrant indicate Annexin-positive/PI-positive, late apoptotic or necrotic cells.Abbreviations: FITC, fluorescein isothiocyanate; PI, propidium iodide; h, hours.
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f3-dddt-9-5987: Progesterone induces mild chromatin condensation and apoptosis.Notes: MCF-7 cells induced by progesterone for 24, 48, and 72 hours were stained with (A) Hoechst 33342 nuclear staining for chromatin condensation and viewed under an Eclipse E-600 fluorescence microscope (×400). (B) Annexin V-FITC/PI double-stained cells were used to assess apoptosis/necrosis by flow cytometry. Cells in the lower right quadrant indicate Annexin-positive/PI-negative, early apoptotic cells. The cells in the upper right quadrant indicate Annexin-positive/PI-positive, late apoptotic or necrotic cells.Abbreviations: FITC, fluorescein isothiocyanate; PI, propidium iodide; h, hours.

Mentions: To further understand whether the concentration of progesterone that induced TOB-1 expression in MCF-7 cells simultaneously induced apoptotic changes, chromatin condensation and apoptosis were assessed in progesterone-treated samples by fluorescence-activated cell sorting analyses. As shown in Figure 3A, Hoechst 33342-stained MCF-7 cells treated with progesterone at a significant concentration for 24, 48, and 72 hours showed less significant nuclear chromatin condensation. This result was further confirmed by Annexin V-FITC/PI double staining (Figure 3B). Annexin V-positive/PI-negative cells were regarded as early apoptotic cells, while Annexin V-positive and PI-positive cells were regarded as late apoptotic or necrotic cells. As shown in Figure 3B, we only observed mild apoptosis or necrosis in progesterone-treated cells.


Progesterone regulates the proliferation of breast cancer cells - in vitro evidence.

Azeez JM, Sithul H, Hariharan I, Sreekumar S, Prabhakar J, Sreeja S, Pillai MR - Drug Des Devel Ther (2015)

Progesterone induces mild chromatin condensation and apoptosis.Notes: MCF-7 cells induced by progesterone for 24, 48, and 72 hours were stained with (A) Hoechst 33342 nuclear staining for chromatin condensation and viewed under an Eclipse E-600 fluorescence microscope (×400). (B) Annexin V-FITC/PI double-stained cells were used to assess apoptosis/necrosis by flow cytometry. Cells in the lower right quadrant indicate Annexin-positive/PI-negative, early apoptotic cells. The cells in the upper right quadrant indicate Annexin-positive/PI-positive, late apoptotic or necrotic cells.Abbreviations: FITC, fluorescein isothiocyanate; PI, propidium iodide; h, hours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644174&req=5

f3-dddt-9-5987: Progesterone induces mild chromatin condensation and apoptosis.Notes: MCF-7 cells induced by progesterone for 24, 48, and 72 hours were stained with (A) Hoechst 33342 nuclear staining for chromatin condensation and viewed under an Eclipse E-600 fluorescence microscope (×400). (B) Annexin V-FITC/PI double-stained cells were used to assess apoptosis/necrosis by flow cytometry. Cells in the lower right quadrant indicate Annexin-positive/PI-negative, early apoptotic cells. The cells in the upper right quadrant indicate Annexin-positive/PI-positive, late apoptotic or necrotic cells.Abbreviations: FITC, fluorescein isothiocyanate; PI, propidium iodide; h, hours.
Mentions: To further understand whether the concentration of progesterone that induced TOB-1 expression in MCF-7 cells simultaneously induced apoptotic changes, chromatin condensation and apoptosis were assessed in progesterone-treated samples by fluorescence-activated cell sorting analyses. As shown in Figure 3A, Hoechst 33342-stained MCF-7 cells treated with progesterone at a significant concentration for 24, 48, and 72 hours showed less significant nuclear chromatin condensation. This result was further confirmed by Annexin V-FITC/PI double staining (Figure 3B). Annexin V-positive/PI-negative cells were regarded as early apoptotic cells, while Annexin V-positive and PI-positive cells were regarded as late apoptotic or necrotic cells. As shown in Figure 3B, we only observed mild apoptosis or necrosis in progesterone-treated cells.

Bottom Line: Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome.Therefore, we further functionally characterized the protein product of TOB-1 in vitro.These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.

ABSTRACT
Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome. From previous studies, we identified differentially expressed genes in each menstrual cycle phase by microarray, then subjected them to functional in vitro analyses. Microarray studies disclosed genes that are upregulated in the luteal phase and follicular phase. TOB-1 is a tumor suppressor gene and was expressed exclusively in the luteal phase in our microarray study. Therefore, we further functionally characterized the protein product of TOB-1 in vitro. To our knowledge, no studies have yet been conducted on reactive oxygen species-regulated tumor suppressor interactions in accordance with the biphasic nature of progesterone. This work demonstrates that progesterone can produce reactive oxygen species in MCF-7 cells and that TOB-1 exerts a series of non-genomic interactions that regulate antiproliferative activity by modulating the antioxidant enzyme superoxide dismutase. Furthermore, this study implicates PTEN as an interacting partner for TOB-1, which may regulate the downstream expression of cell cycle control protein p27 via multiple downstream signaling pathways of progesterone through a progesterone receptor, purely in a time- and concentration-dependent manner. These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival.

No MeSH data available.


Related in: MedlinePlus