RESUMEN
Loss of cell polarity and disruption of tissue organization are key features of tumorigenesis that are intrinsically linked to spindle orientation. Epithelial tumors are often characterized by spindle orientation defects, but how these defects impact tumor formation driven by common oncogenic mutations is not fully understood. Here, we examine the role of spindle orientation in adult epidermis by deleting a key spindle regulator, LGN, in normal tissue and in a PTEN-deficient mouse model. We report that LGN deficiency in PTEN mutant epidermis leads to a threefold increase in the likelihood of developing tumors on the snout, and an over 10-fold increase in tumor burden. In this tissue, loss of LGN alone increases perpendicular and oblique divisions of epidermal basal cells, at the expense of a planar orientation of division. PTEN loss alone does not significantly affect spindle orientation in these cells, but the combined loss of PTEN and LGN fully randomizes basal spindle orientation. A subset of LGN- and PTEN-deficient animals have increased amounts of proliferative spinous cells, which may be associated with tumorigenesis. These results indicate that loss of LGN impacts spindle orientation and accelerates epidermal tumorigenesis in a PTEN-deficient mouse model.
Asunto(s)
Epidermis , Huso Acromático , Animales , Ratones , Huso Acromático/genética , Células Epidérmicas , Carcinogénesis , Polaridad Celular/genéticaRESUMEN
Purpose: Ionizing radiation has been extensively used for medical diagnosis since its discovery in 1895; however, excessive use can lead to deleterious effects. Prior knowledge on radiological protocols based on simulations would be a practical tool for optimal use of radiation. Materials and Methods: Scan length of the thorax was measured from computed tomography (CT) topographic images and cross-sections at three levels of the thorax were measured from tomographic images of 500 adults and 340 children who had undergone CT thorax examinations using Centricity workstation software. The effective diameter (ED) of the thorax was calculated from anterio-posterior (AP) and transverse anatomical dimensions. Results: A 17% increase in scan length was observed for 6-10 years age group compared to 0-5 years, whereas there was marginal increase for 11-15 years of age. A 11.5% increase was observed for 16-18 years compared to 11-15 years age group. The cross-sectional phantom dimensions were calculated from ED measurements obtained from three regions of the thorax. Conclusions: This study has provided age- and gender-specific reference scan lengths, AP and transverse dimensions and ED for radiological examinations of the thorax. This information is useful to develop age- and gender-specific preset protocols and fabricate phantoms of the thorax for the pediatric and adult Indian population.