Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells

Abstract

SCC-S2/GG2-1/NDED is a recently discovered antiapoptotic molecule induced by the activation of the transcription factor NF-kappaB. Here we have examined a role of SCC-S2 in cell growth regulation in vitro and in vivo. Western blotting using an antipeptide antibody revealed endogenous SCC-S2 as a approximately 21 kDa cytosolic protein in human breast cancer cells (MDA-MB 231) and renal carcinoma cells (RCC-RS). The immunofluorescence detection method showed the cytosolic localization of FLAG-tagged human SCC-S2 in COS-1 transfectants. MDA-MB 435 human cancer cells stably transfected with the FLAG-tagged SCC-S2 cDNA exhibited increased growth rate as compared to control vector transfectants, as measured by the cell viability (>twofold; n=3; P<0.005) and thymidine-labeling procedures ( approximately sixfold; n=3; P<0.0001). SCC-S2 transfectants also displayed an increase in cell migration in collagen I as compared to control transfectants ( approximately twofold; n=3; P<0.005). In athymic mice, SCC-S2 transfectants showed significantly enhanced tumor growth as compared to control transfectants (mean tumor volumes, day 16: control, 56.86+/-19.82 mm(3); SCC-S2, 127.54+/-18.78 mm(3); n=5; P<0.03). The examination of a limited number of clinical specimens revealed higher expression levels of SCC-S2 protein in certain human tumor tissues as compared to the matched normal adjacent tissues. Taken together, the present studies demonstrate SCC-S2 as a novel oncogenic factor in cancer cells.

Expression of Tumor Necrosis Factor-alpha-induced Protein 8 in Pancreas Tissues and its Correlation with Epithelial Growth Factor Receptor Levels

“…Overexpression of TNFAIP8 is associated with enhanced cell survival and inhibition of activities of the apoptotic enzymes caspase-8 and caspase-3. TNFAIP8 protein expression, examined by western blot analysis, was found to be higher in several human breast carcinomas (10 cases) and renal cell carcinomas (9 cases) compared to matched normal adjacent tissues (Kumar et al, 2004). These data suggest that TNFAIP8 may function as an oncoprotein in human malignancies.…”

“…proliferation and inhibition of activities of the apoptotic enzymes caspase 8 and caspase 3 (You et al, 2001;Romanuik et al, 2009). Human breast cancer cells transfected with TNFAIP8 increased proliferation, cell migration, and tumor growth rate (Kumar et al, 2004). Knocking down of TNFAIP8 expression in tumor cells reduces their tumorigenicity, suggesting that it may play a role in oncogenesis (Zhang et al, 2006).…”

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

“…It was originally known as SCC-C2, as it was found in a cell line derived from metastatic head and neck squamous cell cancer and was determined to be a negative regulator of apoptosis in overexpression assays. 17,20,25 Its expression levels correlate with the tumor, node, metastasis (TNM) staging of esophageal squamous cell carcinoma, 26 and a similar pattern has been observed in pancreatic cancer, 27 gastric adenocarcinoma 28 and endometrial cancer. 29 It is also a risk factor for non-Hodgkin's lymphoma, and high levels of TNFAIP8 expression are associated with more aggressive forms of epithelial ovarian cancer with poor survival rates 22,30 as well as with non-small cell lung cancer (NSCLC).…”

“…29 It is also a risk factor for non-Hodgkin's lymphoma, and high levels of TNFAIP8 expression are associated with more aggressive forms of epithelial ovarian cancer with poor survival rates 22,30 as well as with non-small cell lung cancer (NSCLC). 31 Furthermore, the overexpression of TNFAIP8 protein in the MDA-MB 435 human breast cancer cell line resulted in increased cell proliferation and cell migration, 17 which was demonstrated to enhance tumorgenicity 32 when injected in athymic mice. In contrast, antisense inhibition in athymic mice resulted in a decreased incidence of pulmonary metastasis.…”

“…PI3K activation can also activate the STAT3 pathway, which is strongly linked to both inflammation and cancer 14,15 and engages in significant crosstalk with NF-κB signaling. 16 The TIPE (tumor necrosis factor-α-induced protein 8-like, or TNFAIP8L) family are newly described regulators of immunity and tumorigenesis 17,18 that are the only known transfer proteins of the lipid second messengers PIP2 and PIP3 19 which are central to Gβγ signaling. Four highly homologous mammalian family members have been identified: TNFAIP8 (tumor necrosis factor-α-induced protein 8); TIPE1 (TNFAIP8L1); TIPE2 (TNFAIP8L2); and TIPE3 (TNFAIP8L3).…”