The oncogene Lysosome-associated protein transmembrane-4β (LAPTM4B) gene was identified, and the polymorphism region in the 5′-UTR of this gene was certified to be associated with tumor susceptibility. LAPTM4B-35 protein was found to be highly expressed in various solid tumors and could be a poor prognosis marker. The functions of LAPTM4B in solid tumors were also explored. It is suggested that LAPTM4B could promote the proliferation of tumor cells, boost invasion and metastasis, resist apoptosis, initiate autophagy and assist drug resistance.
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression. Its transcript is up-regulated in various types of solid tumors including breast cancer. However, its transcriptional regulation mechanism is still unclear. To investigate the mechanism of transcriptional regulation of LAPTM4B in human breast cancer cells, a series of luciferase reporter constructs and construct with mutated binding site for cAMP responsive element binding protein-1 (CREB1) were generated by PCR amplification and transiently transfected into breast cancer cells to determine the transcriptional activities of different promoter regions. The +10∼+292 promoter region was possessed the highest transcriptional activity. The ability of CREB1 to bind the LAPMT4B promoter was confirmed by electrophoretic mobility shift assay, super-shift and RNA interference experiments. Our study identified the core promoter region responsible for constitutive expression of LAPTM4B and clarified that CREB1 played an important role in LAPTM4B transcriptional regulation in human breast cancer cells.
BackgroundLynch syndrome (LS) is caused by mutations in DNA mismatch repair (MMR) genes, which accounts for 3–5% of colorectal cancer. The risks of several types of cancer are greatly increased among individuals with LS. In this study, 4 members of a Chinese family with a MLH1 pathogenic variant, resulting in colonic carcinoma, was reported.Case presentationA 52-year-old colon cancer female was brought to us with a family history of colon cancer. Genetic counseling traced 4 members in her family with colon cancer (mother and 3 siblings including the proband) as well as other cancer types. Next generation sequencing (NGS) with a multiple gene panel including MMR genes showed a germline mutation in MLH1 (c.1852_1854delAAG, p.K618del) in all 3 affected family members and confirmed the diagnosis of Lynch syndrome. In addition, this mutation was also identified in a asymptomatic offspring, who was then recommended to a prophylactic measure against cancer. A personalized health care plan was implemented for monitoring the condition and progression of the affected individuals.ConclusionBased on public database searching followed by pedigree verification, p.K618del variant in MLH1 is a pathogenic mutation, which supported the diagnosis of LS. This case highlights the importance of diagnosis and management in patients with hereditary cancer syndromes, particularly for asymptomatic family members.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0605-x) contains supplementary material, which is available to authorized users.
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