title: In vivo and in vitro studies on apoptosis in OSE cells and inclusion cysts of pregnant heifers.
abstract: Elevated progesterone concentration during pregnancy and use of progesterone-like contraceptives are known to reduce ovarian cancers. This study was undertaken to decipher whether or not there is any relationship between progesterone (also oestrogen)-mediated ovarian surface epithelium (OSE) apoptosis and expression of p53, a cell-cycle arresting protein and potential tumour suppressor. Immunohistochemical staining with cytokeratin confirmed epithelial nature of the cells in the OSE layer and inclusion cysts that invaginate inside stroma after ovulation takes place. The in situ apoptosis index was determined during oestrus, and at mid and late-pregnancy stages in heifers. Epithelia of both tissues exhibited significantly high nuclear staining, suggesting that these cells are aiming to apoptotic destruction. To further establish a role of progesterone, the OSE cells were exposed in vitro to two concentrations of oestrogen and progesterone. It was revealed that progesterone at both concentrations and oestrogen only at high concentration converted a large proportion of these cells apoptotic. The stimulatory effect of progesterone (and to some extent oestrogen) was also seen on p53 expression in the same cultivated OSE cells. The steroid dosage dependence for apoptosis and p53 expression was also somewhat similar. Assuming that progesterone action is mediated through p53-caused apoptosis as a mechanism to evade malignant transformation of OSE cells, p53 expression at mRNA and protein level was investigated in the OSE layer in proximity to stroma, antrum and corpus luteum (CL). In cycling animals CL produces a large amount of progesterone and also oestrogen to maintain the post-ovulatory cycle and to suppress the gonadotropin production. Hence, cells undergoing re-epithelialization and which are in contact with CL were expected to undergo maximum apoptotic modification. Indeed we got the maximum p53/p53 gene expression in these cells. We conclude that progesterone during cycling and pregnancy may reduce the risk of developing ovarian cancer by ceasing cell cycle and diverting damaged and mutagenized OSE cells for apoptosis, and the process may be mediated through elevated p53 synthesis. However, it is also possible that progesterone and p53-induced apoptosis may be entirely different cancer suppressive actions but coincidently happening together.
authors: King Abdulaziz University, P.O. Box 21551, Jeddah 42671, Saudi Arabia.
authors: Salina Y
authors: SY
authors: Saddick
keywords: Ovarian surface epithelium ovarian cancer apoptosis p53
references: J Anim Sci. 1973 Feb;36(2):391-6
references: 4687097
references: Cell. 1997 Feb 7;88(3):323-31
references: 9039259
references: Exp Cell Res. 2004 Sep 10;299(1):248-56
references: 15302591
references: J Natl Cancer Inst. 1998 Dec 2;90(23):1774-86
references: 9839517
references: Cancer. 1993 Jan 15;71(2 Suppl):530-6
references: 8420673
references: Eur J Biochem. 1997 Aug 15;248(1):1-9
references: 9310352
references: J Clin Oncol. 2008 Feb 20;26(6):995-1005
references: 18195328
references: Am J Epidemiol. 2000 Aug 1;152(3):233-41
references: 10933270
references: Int J Oncol. 2000 Mar;16(3):567-76
references: 10675491
references: Cancer Causes Control. 2010 Aug;21(8):1193-201
references: 20559706
references: Reprod Biol Endocrinol. 2010 Aug 21;8:100
references: 20727192
references: J Natl Cancer Inst. 1983 Oct;71(4):717-21
references: 6578367
references: Cancer Res. 2007 Sep 15;67(18):8433-8
references: 17823410
references: Zhonghua Fu Chan Ke Za Zhi. 2000 Jul;35(7):423-6
references: 11776191
references: Lancet. 1971 Jul 17;2(7716):163
references: 4104488
references: Toxicol Pathol. 2007 Jun;35(4):495-516
references: 17562483
references: Anim Reprod Sci. 2007 Apr;98(3-4):271-81
references: 16650698
references: Gynecol Oncol. 2008 Sep;110(3):452-4
references: 18603285
references: Endocr Rev. 2001 Apr;22(2):255-88
references: 11294827
references: Reprod Domest Anim. 2002 Oct;37(5):291-3
references: 12354182
references: J Reprod Fertil. 1988 Mar;82(2):827-41
references: 2834552
references: Anat Histol Embryol. 2006 Oct;35(5):334-42
references: 16968254
references: Oncogene. 2009 Jan 15;28(2):209-18
references: 18836486
references: Anat Rec. 1994 Nov;240(3):322-6
references: 7825729
references: Cancer. 1997 May 15;79(10):1944-50
references: 9149021
references: Gynecol Oncol. 1999 Aug;74(2):265-71
references: 10419743
references: BMC Cancer. 2007 Dec 11;7:223
references: 18070364
references: Int J Fertil Menopausal Stud. 1995;40 Suppl 1:40-53
references: 7581588