cAMP response element-binding (CREB) signalling and ovarian surface epithelial cell survival

O Gubbay, MT Rae, AS McNeilly… - Journal of …, 2006 - joe.bioscientifica.com
O Gubbay, MT Rae, AS McNeilly, FX Donadeu, AJ Zeleznik, SG Hillier
Journal of endocrinology, 2006joe.bioscientifica.com
Ovarian surface epithelial (OSE) cells are targets for hormones and growth factors that
regulate cell proliferation and survival (Murdoch 1995, Auersperg et al. 2001). Repeat
episodes of OSE destruction and regeneration in the vicinity of ovulating follicles are
presumed to explain the high frequency of cancers arising from these cells in human ovaries
(Fathalla 1971, Ozols 1991, Salazar et al. 1996). Understanding post-receptor signalling
pathways through which OSE cell growth and survival are controlled is therefore critical to …
Ovarian surface epithelial (OSE) cells are targets for hormones and growth factors that regulate cell proliferation and survival (Murdoch 1995, Auersperg et al. 2001). Repeat episodes of OSE destruction and regeneration in the vicinity of ovulating follicles are presumed to explain the high frequency of cancers arising from these cells in human ovaries (Fathalla 1971, Ozols 1991, Salazar et al. 1996). Understanding post-receptor signalling pathways through which OSE cell growth and survival are controlled is therefore critical to reproductive health. Ovulation is caused by luteinising hormone (LH) that triggers target ovarian cells to undergo structural and metabolic changes associated with a natural inflammatory process, leading to follicular rupture (Espey 1980, 1994). Although granulosa and theca cells in pre-ovulatory follicles are primary targets for gonadotrophins, OSE cells also express functional receptors for LH and FSH (Kuroda et al. 2001, Parrott et al. 2001, Syed et al. 2001, Gubbay et al. 2004, Choi et al. 2005). A hallmark of post-receptor signalling induced by gonadotrophic hormones in follicular cells is increased intracellular accumulation of cAMP leading to cAMP-dependent protein kinase A (PKA)-mediated phosphorylation of transcription factors, such as cAMP-response element (CRE) binding protein (CREB) and activating transcription factor-1 (ATF1)(Carlone & Richards 1997, Conti 2002). Phosphorylated CREB/ATF1 and related CRE-binding proteins then induce transcription by occupying CREs in the promoter regions of target genes that orchestrate cell proliferation, differentiation and death (Shaywitz & Greenberg 1999, Mayr & Montminy 2001, Impey et al. 2004). Based on previous studies of the role of CREB in granulosa cell survival (Johnson et al. 2001, Aharoni et al. 1995, Somers et al. 1999) and evidence that LH is antiapoptotic in OSE cells (Kuroda et al. 2001, Slot et al. 2006),
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