RRC ID 67462
著者 Morikawa A, Takeuchi T, Kito Y, Saigo C, Sakuratani T, Futamura M, Yoshida K.
タイトル Expression of beclin-1 in the microenvironment of invasive ductal carcinoma of the breast: correlation with prognosis and the cancer-stromal interaction.
ジャーナル PLoS One
Abstract We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome formation in invasive ductal carcinoma of the breast, with a particular focus on the cancer microenvironment. Immunohistochemistry demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1 in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1 in cancer or stromal cells alone did not correlate with patient prognosis. In contrast, loss of beclin-1 in cancer cells and overexpression in stromal mesenchymal cells was associated with local cancer recurrence, postoperative lymph node metastasis, and a poor disease-free survival rate. A comprehensive gene expression analysis was performed on a co-culture of breast cancer cells and mesenchymal stromal cells, that latter of which either expressed beclin-1 or was depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1 in mesenchymal cells co-cultured with breast cancer cells decreased the levels of various pro-inflammatory cytokines, their receptors, and collagen receptors. Quantitative reverse transcription polymerase chain reaction analysis confirmed that reduction of stromal beclin-1 expression decreased the expression of IL-1β and collagen receptor discoidin domain receptor 2 (DDR2). Microenvironmental IL-1β is believed to play an important role in tumor invasion. Recent work has also indicated that overexpression of DDR2 contributes to breast cancer invasion and lymph node metastasis. Taken together, these findings indicate beclin-1 expression in the stroma might be important for shaping the breast cancer microenvironment and thus could be a potent molecular target in patients with invasive ductal carcinoma of the breast.
巻・号 10(5)
ページ e0125762
公開日 2015-1-1
DOI 10.1371/journal.pone.0125762
PII PONE-D-14-50358
PMID 25955408
PMC PMC4425636
MeSH Apoptosis Regulatory Proteins / antagonists & inhibitors Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* Beclin-1 Breast Neoplasms / metabolism Breast Neoplasms / pathology* Carcinoma, Ductal, Breast / metabolism Carcinoma, Ductal, Breast / pathology* Cells, Cultured Coculture Techniques Cytokines / metabolism Discoidin Domain Receptors Disease-Free Survival Female Humans Immunohistochemistry Interleukin-10 Receptor beta Subunit / metabolism Interleukin-1beta / genetics Interleukin-1beta / metabolism Lymphatic Metastasis MCF-7 Cells Membrane Proteins / antagonists & inhibitors Membrane Proteins / genetics Membrane Proteins / metabolism* Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / metabolism Neoplasm Recurrence, Local Prognosis RNA Interference RNA, Small Interfering / metabolism Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism Receptors, Cytokine / metabolism Receptors, Mitogen / genetics Receptors, Mitogen / metabolism Tumor Microenvironment
IF 2.74
リソース情報
ヒト・動物細胞 UE6E7T-2(RCB2153)