Abstract
Сancer-testis antigens (CTAs) comprise proteins which are aberrantly expressed in various malignancies, yet under normal situation are restricted to only germ cells. Semenogelins 1 and 2 (SEMG1 and 2, respectively) belong to the family of non-X-linked (autosomal) cancer-testis antigens. They are the major protein ingredients of human semen and share 78% of similarity between them on the gene level. SEMG1/2 gene products regulate the motility and fertility of sperm, as well as provide sperm the antibacterial defense. Besides, SEMG1 and SEMG2 were detected in various malignancies including small cell lung cancer (SCLC). However, the biological role of both SEMG1 and 2 proteins in tumorigenesis has not been fully understood. We demonstrate here that SEMG1 and SEMG2 (SEMGs) exhibit different patterns of expression and sub-cellular localization in non-small cell lung cancer (NSCLC) cell lines. To elucidate the biological properties of SEMGs in NSCLC, we established H1299 cell lines that were stably transduced with either SEMGs-overexpressing or knockdown vectors, respectively. Using fluorescence-based dihydroethidium (DHE) assay we showed that both SEMGs augmented the production of reactive oxygen species (ROS) up to 2 times. Moreover, SEMGs (especially SEMG1) strongly increased the number of Annexin V–positive apoptotic cells manifesting an increased sensitivity to genotoxic drugs including doxorubicin, etoposide, and cisplatin. Taken our results together, SEMGs may arguably play a positive role in tumorigenesis by sensitizing NSCLCs to genotoxic therapy.
Highlights
Introduction Semenogelins1 and 2 are referred to Cancer-TestisAntigens (CTAs) and represent a group of proteins which are frequently expressed in various neoplasms but normally are restricted to germ cells[1].CTAs are frequently associated with aggressive tumors at the late stage of their development[2,3,4]
To expand our knowledge on SEMGs expression in non-small cell lung cancer (NSCLC) on the protein level, we decided to check the presence of highly homologous SEMG1 and SEMG2 proteins (Fig. 1a) in the panel of 5 adenocarcinoma and 1 squamous cell carcinoma NSCLC cell lines
We decided to examine the subcellular localization of SEMGs in our NSCLC cell lines
Summary
Antigens (CTAs) and represent a group of proteins which are frequently expressed in various neoplasms but normally are restricted to germ cells[1]. CTAs are frequently associated with aggressive tumors at the late stage of their development[2,3,4]. Due to the immune privilege status of the testis tissue, the reexpression of CTAs in tumors often induces strong immune response. This makes CTAs perspective candidates for immunotherapy[5]. In normal cells the expression of CTAs is silenced by methylation[6] and is re-activated in cancer due to hypomethylation of the corresponding loci
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