Background:The overexpression of oestrogen-related receptor-β (ERRβ) in breast cancer patients is correlated with improved prognosis and longer relapse-free survival, and the level of ERRβ mRNA is inversely correlated with the S-phase fraction of cells from breast cancer patients.Methods:Chromatin immunoprecipitation (ChIP) cloning of ERRβ transcriptional targets and gel supershift assays identified breast cancer amplified sequence 2 (BCAS2) and Follistatin (FST) as two important downstream genes that help to regulate tumourigenesis. Confocal microscopy, co-immunoprecipitation (CoIP), western blotting and quantitative real-time PCR confirmed the involvement of ERRβ in oestrogen signalling.Results:Overexpressed ERRβ induced FST-mediated apoptosis in breast cancer cells, and E-cadherin expression was also enhanced through upregulation of FST. However, this anti-proliferative signalling function was challenged by ERRβ-mediated BCAS2 upregulation, which inhibited FST transcription through the downregulation of β-catenin/TCF4 recruitment to the FST promoter. Interestingly, ERRβ-mediated upregulation of BCAS2 downregulated the major G1-S transition marker cyclin D1, despite the predictable oncogenic properties of BCAS2.Interpretation:Our study provides the first evidence that ERRβ, which is a coregulator of ERα also acts as a potential tumour-suppressor molecule in breast cancer. Our current report also provides novel insights into the entire cascade of ERRβ signalling events, which may lead to BCAS2-mediated blockage of the G1/S transition and inhibition of the epithelial to mesenchymal transition through FST-mediated regulation of E-cadherin. Importantly, matrix metalloprotease 7, which is a classical mediator of metastasis and E-cadherin cleavage, was also restricted as a result of ERRβ-mediated FST overexpression.
A 35-year-old man presented with a recurrent temporal conjunctival mass (25 × 12 mm) involving about six-clock hours of the limbus in the left eye. The mass encroached onto the temporal half of cornea and showed surface keratin, large intrinsic and feeder vessels. It infiltrated the deep corneal stroma. There were no cells in the anterior chamber. Ultrasound biomicroscopy confirmed infiltration of deep corneal stroma without intraocular invasion. Surgery involved excision of the conjunctival component with 4-mm margin, lamellar sclerectomy and a penetrating sclerokeratoplasty with 3 mm of healthy corneal margin. Cryotherapy (double-freeze-thaw) was done to the conjunctival margins. Histopathology showed it to be invasive sebaceous cell carcinoma. A thin layer of deep corneal stroma and all conjunctival margins were uninvolved. At thirty-six weeks after treatment the left eye recorded a visual acuity of finger counting at 1 meter distance and no recurrence.
Multicentric cardiac myxoma is a rare syndrome; usually it is familial. We report a rare case of sporadic right atrium (RA) and right ventricle (RV) myxoma in a 26-year-old female presenting to our hospital for the evaluation of sudden onset of dyspnea and left precordial pain attributed to the embolization of degenerating tumor fragments to the pulmonary artery (PA). The exact incidence of sporadic multicentric RA and RV myxoma presenting as acute pulmonary embolism is unknown as multicentric RA and RV myxoma are very rare. Myxomas presenting as pulmonary embolism is <10%. Majority of cardiac myxomas present as exertional dyspnea, chest pain, positional syncope, fever, weight loss and other constitutional symptoms. Any young patient presenting with acute onset dyspnea with multiple cardiac masses may have tumor embolization to the PA diagnosis with transthoracic echocardiography and high-resolution computed tomography of thorax, fast-tracks patient transfer for urgent cardiac surgery to prevent further embolization.
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