title: Progesterone regulates the proliferation of breast cancer cells - in vitro evidence.
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.
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Juberiya M
authors.initials: JM
authors.lastname: Azeez
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Hima
authors.initials: H
authors.lastname: Sithul
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Indhu
authors.initials: I
authors.lastname: Hariharan
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Sreeja
authors.initials: S
authors.lastname: Sreekumar
authors.affiliation: Division of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, India.
authors.forename: Jem
authors.initials: J
authors.lastname: Prabhakar
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Sreeharshan
authors.initials: S
authors.lastname: Sreeja
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Madhavan Radhakrishna
authors.initials: MR
authors.lastname: Pillai
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008183:Luteal Phase / Q000502:physiology; D061986:MCF-7 Cells; D046228:Microarray Analysis; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D011980:Receptors, Progesterone; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011374:Progesterone; D013482:Superoxide Dismutase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: TOB-1; cell growth arrest; progesterone; reactive oxygen species