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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

Cell cycle arrest by progesterone.Notes: Propidium iodide staining was performed in MCF-7 cells without treatment (A), and treated with progesterone for 24 hours (B), 48 hours (C), and 72 hours (D). Samples were then analyzed by flow cytometry. At 72 hours, cells accumulate in the sub G1 phase, indicating cell cycle arrest.
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f4-dddt-9-5987: Cell cycle arrest by progesterone.Notes: Propidium iodide staining was performed in MCF-7 cells without treatment (A), and treated with progesterone for 24 hours (B), 48 hours (C), and 72 hours (D). Samples were then analyzed by flow cytometry. At 72 hours, cells accumulate in the sub G1 phase, indicating cell cycle arrest.

Mentions: As progesterone-treated cells showed only mild apoptosis, we confirmed that the progesterone influence on cell growth was due to the cell cycle. Cell cycle analysis by flow cytometry after 48 hours indicated that progesterone-treated cells showed accumulation in the sub-G1 phase (Figure 4). Reports have implicated cell cycle inhibitor p27 as a negative regulator of G1 progression, which in turn controls cyclin D1 expression.26


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)

Cell cycle arrest by progesterone.Notes: Propidium iodide staining was performed in MCF-7 cells without treatment (A), and treated with progesterone for 24 hours (B), 48 hours (C), and 72 hours (D). Samples were then analyzed by flow cytometry. At 72 hours, cells accumulate in the sub G1 phase, indicating cell cycle arrest.
© Copyright Policy
Related In: Results  -  Collection

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

f4-dddt-9-5987: Cell cycle arrest by progesterone.Notes: Propidium iodide staining was performed in MCF-7 cells without treatment (A), and treated with progesterone for 24 hours (B), 48 hours (C), and 72 hours (D). Samples were then analyzed by flow cytometry. At 72 hours, cells accumulate in the sub G1 phase, indicating cell cycle arrest.
Mentions: As progesterone-treated cells showed only mild apoptosis, we confirmed that the progesterone influence on cell growth was due to the cell cycle. Cell cycle analysis by flow cytometry after 48 hours indicated that progesterone-treated cells showed accumulation in the sub-G1 phase (Figure 4). Reports have implicated cell cycle inhibitor p27 as a negative regulator of G1 progression, which in turn controls cyclin D1 expression.26

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