cyclin-d1 and apelin-13-peptide

Apelin-13 is extensively expressed in various tissues, particularly breast tissue. Apelin‑13 has been shown to promote tumor proliferation in various types of cancer, including hepatocellular, lung and ovarian cancer. However, the effect and molecular mechanism of apelin‑13 in breast cancer cells remains unclear. The present study investigated the effect of apelin‑13 on MCF‑7. Therefore, cell proliferation was determined by MTT and flow cytometry analysis. The results revealed that apelin‑13 markedly increased cell proliferation. Transwell assays demonstrated that apelin‑13 increased MCF‑7 cell invasion. Apelin‑13 also markedly increased the expression of cyclin D1, extracellular matrix metalloproteinase‑1 and amplified in breast cancer 1 (AIB1) in a dose‑dependent manner by polymerase chain reaction assays. To study the molecular mechanism, cell proliferation, invasion and cyclin D1 were inhibited by pre‑treatment with 10 µM of PD98059 (ERK(1/2) inhibitor). Western blotting results suggested that apelin‑13 significantly enhances the expression of p‑ERK(1/2) in a concentration‑dependent manner. In conclusion, the results suggest that apelin‑13 promoted MCF-7 cell proliferation and invasion via the ERK1/2/AIB1 signaling pathway.

Topics: Breast; Breast Neoplasms; Cell Proliferation; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins; MAP Kinase Signaling System; Matrix Metalloproteinase 1; MCF-7 Cells; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neoplasm Invasiveness; Nuclear Receptor Coactivator 3; Phosphorylation

The aim of this study was to investigate the role of apelin in the cell proliferation and autophagy of lung adenocarcinoma. The over-expression of APJ in lung adenocarcinoma was detected by immunohistochemistry, while plasma apelin level in lung cancer patients was measured by enzyme-linked immunosorbent assay. Our findings revealed that apelin-13 significantly increased the phosphorylation of ERK1/2, the expression of cyclin D1, microtubule-associated protein 1 light chain 3A/B (LC3A/B), and beclin1, and confirmed that apelin-13 promoted A549 cell proliferation and induced A549 cell autophagy via ERK1/2 signaling. Moreover, there are pores on the surface of human lung adenocarcinoma cell line A549 and apelin-13 causes cell surface smooth and glossy as observed under atomic force microscopy. These results suggested that ERK1/2 signaling pathway mediates apelin-13-induced lung adenocarcinoma cell proliferation and autophagy. Under our experimental condition, autophagy associated with 3-methyladenine was not involved in cell proliferation.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Humans; Intercellular Signaling Peptides and Proteins; Lung Neoplasms; Membrane Proteins; Microtubule-Associated Proteins; Phosphorylation; Signal Transduction

Vascular smooth muscle cells (VSMCs) were prepared from thoracic aortas of male Sprague-Dawley rats by the explant method to observe VSMC proliferation via phosphoinositide 3 kinase (PI3K)/Akt signaling transduction pathway induced by apelin-13. Expression of PI3K, phospho-PI3K, phospho-Akt, ERK1/2, phospho-ERK1/2 and cyclin D1 was detected by western blot analysis. Results showed that apelin-13 promoted the expression of phospho-PI3K and phospho-Akt in dose- and timedependent manner. PI3K inhibitor LY294002 significantly decreased the expression of phospho-PI3K, phospho-Akt, phospho-ERK1/2, and cyclin D1 induced by apelin-13. The Akt inhibitor 1701-1 significantly diminished the expression of phospho-Akt, phospho-ERK1/2, and cyclin D1 stimulated by apelin-13. MTT assay results showed that PI3K inhibitor LY294002 and Akt inhibitor 1701-1 significantly inhibited the VSMC proliferation induced by apelin-13. Apelin-13 promoted VSMC proliferation through PI3K/Akt signaling transduction pathway.

Topics: Animals; Aorta, Thoracic; Apelin Receptors; Blotting, Western; Cattle; Cell Proliferation; Chromones; Cyclin D1; Intercellular Signaling Peptides and Proteins; Male; Morpholines; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Signal Transduction

Apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Vascular smooth muscle cells express both apelin and APJ, which are important regulatory factors in the cardiovascular and nervous systems. Importantly, APJ is also involved in the pathogenesis if HIV-1 infection. We investigated whether vascular smooth muscle cell proliferation was regulated through an apelin-pERK1/2-cyclin D1 signal transduction pathway. Apelin-13 significantly stimulated vascular smooth muscle cell proliferation and increased cell cycle progression. Apelin-13 a decreased the proportion of cell in the G0/G1 phase while increasing the number of cells in S phase. Apelin-13 also increased the levels of cyclin D1, cyclin E and pERK1/2. Treatment of cells with the MEK inhibitor PD98059 attenuated the apelin-3-induced pERK1/2 activation. Similarly, treatment with PD98059 partially diminished the apelin-13-induced expression of cyclin D1 and vascular smooth muscle cell proliferation. Taken together, these data established that apelin-13 stimulates vascular smooth muscle cell proliferation by promoting the G1-S phase transition, and that this effect is mediated in part by an apelin-pERK1/2-cyclin D1 signal cascade.

Topics: Animals; Aorta, Thoracic; Apelin; Carrier Proteins; Cell Culture Techniques; Cell Cycle; Cell Division; Cells, Cultured; Cyclin D1; Flow Cytometry; Humans; Infections; Intercellular Signaling Peptides and Proteins; Male; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley