Survivin Gene Expression in Endometriosis

Abstract

Survivin is a novel inhibitor of apoptosis and is expressed during fetal development and in cancer tissues, but its expression has not been reported in normal adult tissues or benign diseases. We investigated survivin gene and protein expression in a tumor-like benign disease, endometriosis, and correlated them with apoptosis and invasive phenotype of endometriotic tissues. Gene expression levels of survivin, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1 (MT1)-MMP in 63 pigmented or nonpigmented endometriotic tissues surgically obtained from 35 women with endometriosis were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. Survivin, MMP-2, MMP-9, and MT1-MMP mRNA expression levels in clinically aggressive pigmented lesions were significantly higher than those in normal eutopic endometrium, and survivin gene expression in pigmented lesions was also higher than that in nonpigmented lesions (P < 0.05). There was a close correlation between survivin and MMP-2, MMP-9, or MT1-MMP gene expression levels in 63 endometriotic tissues examined (P < 0.01). Apoptotic cells detected by the dUTP nick-end labeling were rare in 11 ovarian endometriotic tissues, which showed positive immunohistochemical expression for survivin and MMPs. Our findings suggest that up-regulation of survivin and MMPs may cooperatively contribute to survival and invasion of endometriosis.

The expression of HER-2/neu (c-erbB2), survivin and cycline D1 in serous ovarian neoplasms: their correlation with clinicopathological variables

“…Survivin, as a strong anti-apoptotic protein, has been demonstrated in fetal development, endometriosis and secretory phase of endometrium (Ambrosini et al 1997;Ueda et al 2002;Konno et al 2000). Whereas overexpression was found to be related with the aggressiveness of the tumor and resistance to chemotherapy and/or radiation (Zaffaroni et al 2002).…”

Endometriosis and the neoplastic process

“…Similarly, endometriotic lesions have also evolved strategies to evade apoptosis by: (i) increased Bcl-2, and decreased BAX (Meresman et al 2000); (ii) upregulation of survivin and matrix metalloproteinases (MMPs) (Ria et al 2002, Ueda et al 2002a; (iii) elevated soluble Fas ligand (FasL) and interleukin (IL)-8 in endometriotic peritoneal fluid (the increased FasL expression by IL-8 may induce apoptosis of T lymphocytes and thus enable endometriosis to evade immune-mediated cell death (Garcia-Velasco et al 2002)); and (iv) germline (Chang et al 2002) and somatically acquired (Bischoff et al 2002) inactivating mutations of p53 gene.…”

Effects of Danchi decoction on P450AROM, survivin of eutopic endometrium of patients with endometriosis after conservative surgery

“…Thanks to these characteristics different from other proteins, it has attracted wide interest. Investigations of Ueda et al (2002) showed that the expression of survivin in ectopic lesions of the endometrium was higher than that in the normal one. They also found that the expression of survivin in pigmented lesions was higher than the non-pigmented lesions.…”