TGFBR1 Signaling and Breast Cancer

Abstract

Over the past decade mutations discovered in genes such as BRCA1, BRCA2, TP53 and PTEN, have emerged as high-penetrance susceptibility genes and are clinically relevant for determination of breast cancer risk. Genetic counseling and subsequent screening for mutations and gene rearrangement has improved patient outcome through early detection and prophylactic interventions in patients with familial breast cancer syndromes. However, these high-penetrance genes only account for a small fraction of the hereditary linked breast cancers. It is currently believed that low-penetrance susceptibility alleles and/or environmental factors may play an important role in the remaining cases. TGFBR1*6A (*6A) is a common hypomorphic variant of the type I TGF-β receptor gene (TGFBR1) that has been associated with risk for several forms of cancer, in particular breast cancer. Several epidemiological studies have suggested that patients who carry the *6A allele have an increased risk of breast cancer. Furthermore, functional analysis suggests that this mutation alters TGF-β signaling and promotes tumorigenesis. Although a decade of research has provided basic information in regards to the prevalence of this mutation in several cancer types and populations the molecular underpinning of its functional effects are poorly understood. A better understanding of the molecular mechanism of TGFBR1 signaling in breast cancer may have an impact on breast cancer risk assessment and breast cancer prevention.

CCL2/CCR2 Chemokine Signaling Coordinates Survival and Motility of Breast Cancer Cells through Smad3 Protein- and p42/44 Mitogen-activated Protein Kinase (MAPK)-dependent Mechanisms

“…Given the importance of autocrine TGF-␤ signaling in breast cancer cells (67,68), we evaluated the possibility that CCL2 signaling was dependent on TGF-␤ expression. 4T1 mammary carcinoma cells were treated with neutralizing antibodies to TGF-␤ in the presence or absence of CCL2.…”

Experimental verification of a conserved intronic microRNA located in the human TrkC gene with a cell type-dependent apoptotic function

“…HBEGF is a known growth factor that is potentially involved in cell cycle [34]. TGbR1 as a TrkC-miR1-3p predicted target gene is involved in multiple opposite cellular processes such as apoptosis and proliferation [35,36]. There are multiple highly conserved MREs for TrkC-miR1-5p within the 3 0 -UTR sequences of MDN1 and HBEGF genes that may justify its strong effect on these target genes expression detected by qRT-PCR (Fig.…”

“…Also, miRNAs originated from the same precursor as seen for hsa-miR-28 might show opposite functions [48]. Since, predicted targets of TrkC-miR1-5p and TrkC-miR1-3p (HBEGF and TGbR1, respectively) are suggested to be involved in apposite functions of apoptosis and survival [34][35][36], it remained to be tested if the contradictory function of TrkC is related to these miRNAs.…”

Immunotherapy for hepatocellular carcinoma

“…It has dual function: one is to inhibit tumor proliferation and initiate tumor cell differentiation and apoptosis in the early stage of tumorogenesis, the other is its immune suppressive potential in advanced stage disease. Moreover, TGF-β also has capability of angiogenesis promotion and epithelial-mesenchymal transition (EMT) induction (46)(47)(48), which facilitates tumor invasion and metastasis. TGF-β1 is a subtype of TGF-β, and a principal isoform in humans, which is considered as a biomarker for the occurrence and development of tumor.…”