The Human Splice Variant Δ16HER2 Induces Rapid Tumor Onset in a Reporter Transgenic Mouse

Several transgenic mice models solidly support the hypothesis that HER2 (ERBB2) overexpression or mutation promotes tumorigenesis. Recently, a HER2 splice variant lacking exon-16 (Δ16HER2) has been detected in human breast carcinomas. This alternative protein, a normal byproduct of HER2, has an increased transforming potency compared to wild-type (wt) HER2 receptors. To examine the ability of Δ16HER2 to transform mammary epithelium in vivo and to monitor Δ16HER2-driven tumorigenesis in live mice, we generated and characterized a mouse line that transgenically expresses both human Δ16HER2 and firefly luciferase under the transcriptional control of the MMTV promoter. All the transgenic females developed multifocal mammary tumors with a rapid onset and an average latency of 15.11 weeks. Immunohistochemical analysis revealed the concurrent expression of luciferase and the human Δ16HER2 oncogene only in the mammary gland and in strict correlation with tumor development. Transgenic Δ16HER2 expressed on the tumor cell plasma membrane from spontaneous mammary adenocarcinomas formed constitutively active homodimers able to activate the oncogenic signal transduction pathway mediated through Src kinase. These new transgenic animals demonstrate the ability of the human Δ16HER2 isoform to transform “per se” mammary epithelium in vivo. The high tumor incidence as well as the short latency strongly suggests that the Δ16HER2 splice variant represents the transforming form of the HER2 oncoprotein

Crecimiento somático del cangrejo violinista Uca rapax (Smith, 1870) (Brachyura: Ocypodidae) de dos manglares subtropicales de Brasil

The crabs were collected monthly, from April 2001 to March 2002 in the mangroves of Itamambuca and Ubatumirim in Ubatuba, São Paulo, Brazil, using the procedure of catch per unit effort (cpue) during 15 minutes at low tide periods by digging the burrows. The sex and carapace width (mm) were recorded for each crab in a sample of 1 294 crabs in Itamambuca mangrove (667 males and 627 females) and 2 107 crabs in Ubatumirim (1 117 males and 990 females). The somatic growth herein described is based on analysis of frequency distributions in size classes using the von Bertalanffy's growth model. The growth curves based on the carapace width (mm) of males and females are described respectively by the equations: Wt=23.9[1- e-0.21(t+0.87)] and Wt=23.8[1-e-0.16(t+1.18)] in Itamambuca and Wt=21.3[1-e-0.16(t+1.12)] and Wt=20.4[1-e-0..15(t+1.29)] in Ubatumirim mangrove. The crabs from Itamambuca reached their maximum age in 1 620 days (males) and 1 800 days (females), while those from Ubatumirim, required 1 440 days (males) and 1 560 days (females).Los cangrejos se recolectaron mensualmente durante 15 minutos durante el período de marea baja, desde abril 2001 hasta mayo 2002, en los manglares de Itamambuca y de Ubatumirim, en Ubatuba, São Paulo, Brasil. El sexo y el ancho del caparazón (mm) fueron medidos para cada cangrejo en una muestra de 1 294 cangrejos in Itamambuca (667 machos y 627 hembras) y 2 107 cangrejos en Ubatumirim (1 117 machos y 990 hembras). El crecimiento somático fue determinado por medio del análisis de distribucion de frecuencias por clase de talla utilizando el modelo de crecimiento de von Bertalanffy. Las curvas de crecimiento obtenidas para machos y hembras fueron, respectivamente: Wt=23.9[1-e-0.21(t+0.87)] y Wt=23.8[1-e-0.16(t+1.18)] para Itamambuca y Wt=21.3[1-e-0.16(t+1.12)] y Wt=20.4[1-e-0.15(t+1.29)], para Ubatumirim. Los cangrejos violinistas de Itamambuca alcanzan su edad máxima a los 1 620 días (machos) y 1 800 días (hembras), mientras que los de Ubatumirim a los 1 440 días (machos) y a los 1 560 días (hembras)