Speckle-type POZ (pox virus and zinc finger protein) protein gene deletion in ovarian cancer: Fluorescence in situ hybridization analysis of a tissue microarray

Abstract

The aim of the present study was to investigate the status of speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) gene located on chromosome 17q21 in ovarian cancer (OC). The present study evaluated a tissue microarray, which contained 90 samples of ovarian cancer and 10 samples of normal ovarian tissue, using fluorescence hybridization (FISH). FISH is a method where a SPOP-specific DNA red fluorescence probe was used for the experimental group and a centromere-specific DNA green fluorescence probe for chromosome 17 was used for the control group. The present study demonstrated that a deletion of the SPOP gene was observed in 52.27% (46/88) of the ovarian cancer tissues, but was not identified in normal ovarian tissues. Simultaneously, monosomy 17 was frequently identified in the ovarian cancer tissues, but not in the normal ovarian tissues. Furthermore, the present data revealed that the ovarian cancer histological subtype and grade were significantly associated with a deletion of the SPOP gene, which was assessed by the appearance of monosomy 17 in the ovarian cancer samples; the deletion of the SPOP gene was observed in a large proportion of serous epithelial ovarian cancer (41/61; 67.21%), particularly in grade 3 (31/37; 83.78%). In conclusion, deletion of the SPOP gene on chromosome 17 in ovarian cancer samples, which results from monosomy 17, indicates that the SPOP gene may serve as a tumor suppressor gene in ovarian cancer.

<p>SPOP Regulates The Biological Mechanism Of Ovarian Cancer Cells Through The Hh Signaling Pathway</p>

“…Studies on tumors have reported that SPOP may participate in the regulation of cell proliferation and apoptosis in a variety of tumors. Previously, we have found that the SPOP gene locus has a high-frequency deletion or loss of heterozygosity in ovarian cancer 22. However, the role of SPOP in ovarian cancer and its mechanism have remained unclear.…”

“…The differential effect of SPOP in renal clear cell carcinoma and other cancers may be due to differences in the subcellular localization of SPOP in different cancers. In addition, we have previously identified high-frequency LOH in the SPOP locus in ovarian cancer tissues by fluorescence in situ hybridization (FISH) and suggested that SPOP may play a role in ovarian cancer 22. However, such a role and the related mechanisms remain unclear.…”

The emerging role of SPOP protein in tumorigenesis and cancer therapy

“…Only one group indicated that overexpression of the SPOP protein was essential for the apoptosis of HeLa cells, while this proapoptotic function was countered by ablation of SPOP [28]. Furthermore, one study used a tissue microarray to reveal a deletion mutant of SPOP in the majority of OC tissues that was not found in normal ovarian tissues, and this deletion mutant was correlated with high histological type and grade in OC [49]. Similarly, Jiang et al identified several novel mutations in OC cell lines and tissues through wholeexome sequencing, including mutations in SPOP [50].…”

Functional analysis of Cullin 3 E3 ligases in tumorigenesis

“…Protein analysis by Hu et al found that more than 50% of ovarian cancer samples carried loss-of-function mutations of SPOP compared to 0% in adjacent tissues. Meanwhile, an inverse correlation exists between the tumor clinic pathological grade and the positivity of SPOP [201]. With regard to breast cancer, its proliferative and migratory potentials may be restricted due to SPOP-induced degradation on SRC-3 and PR (progesterone receptor) in vitro and in vivo, which usually amplifies the estrogen/progesterone-mediated expansion and dispersion of breast cancer cells [166,202,203].…”

“…Tumor suppressor in gastric cancer [210] Urological system ) and xenografts in nude mouse) [181,196] 2 Tumor promoter in ccRCC (Xenografts in nude mouse) [223] 1 Tumor suppressor in prostate cancer [29] 2 Tumor promoter in ccRCC [223] Gynecological system Physiology Normalizing decidualization of endometrial stromal cells in mice [179] Normalizing decidualization of endometrial stromal cells [179] Tumorigenesis Tumor suppressor in breast cancer (Xenografts in nude mouse) [166] 1 Tumor suppressor in ovarian cancer cells [201] 2 Tumor suppressor in breast cancer cells [203] 3 Tumor suppressor in endometrial cancer cells [205] Musculoskeletal Compounds that directly target Cullin 3-based E3 ligases.…”