BTC

Case study 1: Yuxi Li, 2023

The gap junction protein, connexin 43 (Cx43) is highly expressed in human granulosa-lutein (hGL) cells. The phosphorylation of certain amino acid residues in the Cx43 protein has been shown to be related to a decline in gap junction intercellular communication (GJIC), which subsequently affects oocyte meiotic resumption. As a member of the epidermal growth factor (EGF) family, betacellulin (BTC) mediates luteinizing hormone (LH)-induced oocyte maturation and cumulus cell expansion in mammalian follicles. Whether BTC can regulate Cx43 phosphorylation, which further reduces Cx43-coupled GJIC activity in hGL cells remains to be determined.

The expression levels of Cx43 and phosphorylated Cx43 were examined following cell incubation with BTC at different time points. Real-time-quantitative PCR and western blot analysis were used to detect the specific mRNA and protein levels, respectively. GJIC between SVOG cells were evaluated using a scrape loading and dye transfer assay. The results showed that BTC induced the rapid phosphorylation of Cx43 at serine368 without altering the expression of Cx43 in primary and immortalized hGL cells. BTC promptly induced the phosphorylation of connexin 43 at Ser368, leading to decreased GJIC activity in hGL cells. The BTC-induced cellular activities were most likely driven by the EGFR-mediated PKC-dependent signaling pathway.

Fig1. SVOG cells were treated with 50 ng/ml BTC for different time durations (5, 15, or 40 min), and the levels of phosphorylated Cx43 protein were examined via Western blot analysis.

Fig2. SVOG cells were pretreated with DMSO, 10 μM AG1478 for 40 min, and the cells were then treated with 50 ng/ml BTC for an additional 15 min.

Case study 2: Jianfang Zhao, 2016

Epithelial ovarian cancer is the leading cause of death among gynaecological cancers. Previous studies have demonstrated that epidermal growth factor receptor (EGFR) ligands can induce ovarian cancer cell invasion by down-regulating E-cadherin. Betacellulin is overexpressed in a variety of cancers and is associated with reduced survival. However, the biological functions and clinical significance of betacellulin in ovarian cancer remain unknown.

Treatment of SKOV3 and OVCAR5 ovarian cancer cell lines with betacellulin down-regulated E-cadherin, but not N-cadherin. In addition, betacellulin treatment increased the expression of Snail and Slug, and these effects were completely blocked by pre-treatment with EGFR inhibitor AG1478. Betacellulin treatment induced the activation of both the MEK-ERK and PI3K-Akt signaling pathways, and it also significantly increased ovarian cancer cell migration. Importantly, the effects of betacellulin on E-cadherin, Slug and cell migration were attenuated by pre-treatment with either U0126 or LY294002.

Fig3. Cells were treated for 24 hours without (Ctrl) or with increasing concentrations of betacellulin (BTC: SKOV3, 0.5, 1, 5 or 10 ng/ml; OVCAR5, 1, 10, 20, 50 or 100 ng/ml), E-cadherin and N-cadherin protein levels were examined by Western blot.

Fig4. Betacellulin suppresses E-cadherin via Slug in ovarian cancer cells.

Fig1. Proposed mechanism of BTC-stimulated IL-8 production and bio-behaviors of lung cancer cells. (Lin Shi, 2014)

Fig2. Model showing the mechanism of BTC action in EGFR mutant lung adenocarcinoma. (Suresh Chava, 2022)

BTC involved in several pathways and played different roles in them. We selected most pathways BTC participated on our site, such as ErbB signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with BTC were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

BTC has several biochemical functions, for example, epidermal growth factor receptor binding, growth factor activity, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by BTC itself. We selected most functions BTC had, and list some proteins which have the same functions with BTC. You can find most of the proteins on our site.

BTC has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with BTC here. Most of them are supplied by our site. Hope this information will be useful for your research of BTC.

S100A4; KRT31; GMPPA; ERBB2