Ceramide galactosyltransferase (UGT8) as a molecular marker of canine mammary tumor malignancy

Abstract

Thirty-two canine mammary tubulopapillary carcinomas and 14 simple adenomas were studied by immunohistochemistry for the expression of UDP-galactose:ceramide galactosyltransferase (UGT8). The majority of tissue specimens (57%) representing adenomas had no or weak reaction with anti-UGT8 antibodies (0-2 pts according to IRS scale) in comparison to the majority of carcinomas (90%) which stained with high intensities (3-9 pts according to IRS scale). When the average values of the reaction intensities (IRS) for malignant and benign tumors were compared, using the Mann-Whitney U-test, significant differences in UGT8 expression between them were found (P < 0.001). Mammary tubulopapillary carcinomas were further analyzed by IHC and the same rabbit polyclonal antibody directed against UGT8 according to their malignancy grade. It was found that the level of UGT8 increased in tumor specimens together with their grading. A comparison of the average values of the reaction intensity (IRS scale) revealed a significant difference (Mann-Whitney U-test, P < 0.05) in UGT8 expression between tumors representing malignancy grades G3 and G1. Based on the obtained results, it is proposed that UGT8 is associated with malignancy of canine mammary gland cells and may have a potential value as a diagnostic marker.

The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms

“…UGT8 expression was shown to be upregulated in breast (610,806), ovarian (416), and lung (613) cancer. Moreover, breast cancer cell lines with a luminal epitheliallike phenotype expressed little or no UGT8, while malignant, more mesenchymal-like cells expressed relatively high levels (157,526). Immunohistochemical analyses showed that increased UGT8 expression correlated with increasing breast tumor grade; the same finding was also reported for canine mammary tumors (526).…”

“…Moreover, breast cancer cell lines with a luminal epitheliallike phenotype expressed little or no UGT8, while malignant, more mesenchymal-like cells expressed relatively high levels (157,526). Immunohistochemical analyses showed that increased UGT8 expression correlated with increasing breast tumor grade; the same finding was also reported for canine mammary tumors (526). Recently, UGT8 was listed as part of a six-gene predictive signature for breast cancer metastasis to lung (380).…”

Microbubble-based enhancement of radiation effect: Role of cell membrane ceramide metabolism

“…Fluorescent labelling of sphingolipids was previously used to study their trafficking, uptake, and metabolism, where it was proven to be a powerful tool, specifically in the trafficking of ceramide to the Golgi- apparatus [41, 42]. Furthermore, emerging reports [24, 43, 44] indicated elevated levels of UGT8 in breast cancer and lung metastasis, and have suggested using UGT8 as a biomarker in the cancer prognosis. Nevertheless, no comprehensive molecular analysis of the signaling mechanism of this molecule is available.…”

“…This enzyme is localized to the nuclear envelope and the endoplasmic reticulum and has been reported to act as an anti-apoptotic molecule that affects tumorigenic and metastatic properties of breast cancer cells [22]. UGT8 is also linked to the development of lung metastases and is up-regulated in both ovarian and breast cancers [23–25]. Its anti-apoptotic function is achieved through disruption of the ceramide signalling pathway by converting ceramide into galactosylceramide.…”

A Novel Function for UDP Glycosyltransferase 8: Galactosidation of Bile Acids

“…UGT8 was recently reported to be highly expressed in breast tumors with a malignant phenotype but not in nonmetastatic tumors (Dzięgiel et al, 2010). Several publications now posit UGT8 as a marker of cancer malignancy (Nowak et al, 2013;Owczarek et al, 2013): production of GalCer by UGT8 may alter cancer cell adhesion and also inhibit apoptosis (Beier and Gorogh, 2005;Owczarek et al, 2013).…”