A Genetic Screen for Anchorage-Independent Proliferation in Mammalian Cells Identifies a Membrane-Bound Neuregulin

Anchorage-independent proliferation is a hallmark of oncogenic transformation and is thought to be conducive to proliferation of cancer cells away from their site of origin. We have previously reported that primary Schwann cells expressing the SV40 Large T antigen (LT) are not fully transformed in that they maintain a strict requirement for attachment, requiring a further genetic change, such as oncogenic Ras, to gain anchorage-independence. Using the LT-expressing cells, we performed a genetic screen for anchorage-independent proliferation and identified Sensory and Motor Neuron Derived Factor (SMDF), a transmembrane class III isoform of Neuregulin 1. In contrast to oncogenic Ras, SMDF induced enhanced proliferation in normal primary Schwann cells but did not trigger cellular senescence. In cooperation with LT, SMDF drove anchorage-independent proliferation, loss of contact inhibition and tumourigenicity. This transforming ability was shared with membrane-bound class III but not secreted class I isoforms of Neuregulin, indicating a distinct mechanism of action. Importantly, we show that despite being membrane-bound signalling molecules, class III neuregulins transform via a cell intrinsic mechanism, as a result of constitutive, elevated levels of ErbB signalling at high cell density and in anchorage-free conditions. This novel transforming mechanism may provide new targets for cancer therapy

Pigment degradation in oil paint induced by indoor climate:comparison of visual and computational backscattered electron images

\u3cp\u3eFor the first time the degradation of lead white pigment in mature oil paint has been used as an internal marker for the degree of saponification and hence chemical degradation of oil paint. Computational image analysis of the backscattered electron images quantified the degree of the intact lead white pigment versus the nonpigmented and lead-rich areas (degraded lead white) in the paint layers. This new methodology was applied to a series of paint samples taken from four painted wall hangings (dated 1778), which makes it possible to study the influence of indoor climate on chemical degradation of aged oil paintings. The visual interpretation and computational image analysis of the backscattered electron images revealed clear trends. The highest degree of lead white degradation in the room was found in samples from the north wall close to the windows, whereas degradation diminished further away from the window. Lead white from the south wall was less degraded, but showed a similar trend as in the paintings on the north wall. These results imply a strong relationship between chemical degradation of paint and location of the paint in the room.\u3c/p\u3