Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and serous ovarian tumors

Abstract Background We showed there are specific ALDH1 autoantibodies in ovarian autoimmune disease and ovarian cancer, suggesting a role for ALDH1 in ovarian pathology. However, there is little information on the ovarian expression of ALDH1. Therefore, we compared ALDH1 expression in normal ovary and benign and malignant ovarian tumors to determine if ALDH1 expression is altered in ovarian cancer. Since there is also recent interest in ALDH1 as a cancer stem cell (CSC) marker, we assessed co-expression of ALDH1 with CSC markers in order to determine if ALDH1 is a potential CSC marker in ovarian cancer. Methods mRNA and protein expression were compared in normal human ovary and serous ovarian tumors using quantitative Reverse-Transcriptase PCR, Western blot (WB) and semi-quantitative immunohistochemistry (IHC). ALDH1 enzyme activity was confirmed in primary ovarian cells by flow cytometry (FC) using ALDEFLUOR assay. Results ALDH1 mRNA expression was significantly reduced (p Conclusions Total ALDH1 expression is significantly reduced in malignant ovarian tumors while it is relatively unchanged in benign tumors compared to normal ovary. Thus, ALDH1 expression in the ovary does not appear to be similar to breast, lung or colon cancer suggesting possible functional differences in these cancers. Significance These observations suggest that reduced ALDH1 expression is associated with malignant transformation in ovarian cancer and provides a basis for further study of the mechanism of ALDH1 in this process.</p

Selection of hens with normal ovaries or ovarian tumors using (A–C) color Doppler ultrasound and (D–F) gross morphology of the ovaries.

<p>A normal ovary (<b>A and D</b>) with maturing ovarian follicles (F1, F2) and stromal blood vessels (arrows) with normal gross morphology showing maturing (F1, F2) ovarian follicles. An example of an abnormal ovary (<b>B and E</b>) that contains more blood vessels (arrows) than in the normal ovary, no detectable large mature follicles and a small solid tissue mass (circle) in the ovary. An example of late stage ovarian cancer (<b>C</b>) characterized by a large solid mass with increased blood flow (arrows) and profuse ascites (*).The gross morphology (<b>F</b>) confirmed the presence of multiple solid masses and tumor metastasis to other organs. Abbreviations: CT = cecal tonsil; F1–F2 = large preovulatory follicles; GI = gastrointestinal tract; OV = ovary; S = ovarian stroma; SM = solid tissue mass in the ovary; SP = spleen; UOD = upper oviduct; UT = uterus.</p

Elevated Transglutaminase 2 Activity Is Associated with Hypoxia-Induced Experimental Pulmonary Hypertension in Mice

Previous studies in human patients and animal models have suggested that transglutaminase 2 (TG2) is upregulated in pulmonary hypertension (PH), a phenomenon that appears to be associated with the effects of serotonin (5-hydroxytryptamine; 5-HT) in this disease. Using chemical tools to interrogate and inhibit TG2 activity <i>in vivo</i>, we have shown that pulmonary TG2 undergoes marked post-translational activation in a mouse model of hypoxia-induced PH. We have also identified irreversible fluorinated TG2 inhibitors that may find use as non-invasive positron emission tomography probes for diagnosis and management of this debilitating, lifelong disorder. Pharmacological inhibition of TG2 attenuated the elevated right ventricular pressure but had no effect on hypertrophy of the right ventricle of the heart. A longitudinal study of pulmonary TG2 activity in PH patients is warranted