Srcasm overexpression in psoriasis- insights into pathogenesis Background: Psoriasis is a prevalent, chronic cutaneous disorder associated with a T-cell lymphocytic infiltrate and altered keratino- cyte growth. Some of the molecular features of enhanced keratinocyte growth include increased growth factor receptor activation leading to enhanced cellular tyrosine kinase activity. Receptor tyrosine kinases, including the epidermal growth factor (EGF) receptor, are important regulators of keratinocyte growth, and increased activity of this recep- tor has been detected in psoriasis. A recently discovered, novel regu- lator of Src tyrosine kinases, termed Src-activating and signaling molecule (Srcasm), has been shown to modulate EGF signaling and promote differentiation in human keratinocytes. Given the properties of Srcasm, it would be of interest to characterize its expression in psoriasis. In this study, the levels of Srcasm mRNA and protein are characterized, and the relationship of these experimental observations to the psoriasis pathogenesis is discussed. Methods: The levels of Srcasm mRNA were determined by quantitative reverse transcriptase polymerase chain reaction (RT– PCR) on RNA isolated from unremarkable and lesional patient tissue. These data were supplemented by performing radioactive in situ hybridization on formalin-fixed biopsy specimens of psoriatic lesions and unremarkable epidermis. Expression of Srcasm protein was evaluated by protein immunohistochemistry and Western blotting of protein lysates derived from patient samples. Results: All experimental modalities show that levels of Srcasm mRNA and protein were elevated in psoriatic lesions compared to unremarkable epidermis. Conclusions: Increased levels of Srcasm mRNA and protein are seen in psoriasis. Given what is known regarding Srcasm function, increased levels of this molecule in keratinocytes may represent a cell compensatory mechanism that is primed to re-establish a physiologic differentiation program. Pulitzer M, Li W, Hanson M, Singh F, Elenitsas R, Gelfand JM, VanVoorhees A, Seykora JT. Srcasm overexpression in psoriasis- insights into pathogenesis. J Cutan Pathol 2007; 34: 160–165. # Blackwell Munksgaard 2006. Melissa Pulitzer * , Weijie Li * , Matthew Hanson, Fiza Singh, Rosalie Elenitsas, Joel M. Gelfand, Abby VanVoorhees and John T. Seykora Department of Dermatology, University of Pennsylvania Medical School, Philadelphia, PA, USA John T. Seykora, MD, PhD, Assistant Professor, Department of Dermatology, University of Pennsylvania Medical Center, 235 A CRB, 415 Curie boulevard, Philadelphia, PA 19104, USA Tel: þ1 215 8980170 Fax: þ1 215 5732143 e-mail: john.seykora@uphs.upenn.edu Accepted for publication February 27, 2006 Psoriasis is a chronic, papulosquamous, cutaneous disorder affecting greater than 2% of the adult population. 1,2 One characteristic feature of the psor- iatic epidermis is the hyperplasia associated with increased keratinocyte proliferation; increased keratinocyte proliferation is associated with a shor- tened cell cycle, altered differentiation, and an increased percentage of keratinocytes capable of undergoing cell division. 3 Another key feature of psoriasis is a lymphocytic infiltrate containing T-cell helper type 1 cells that produce g-interferon, interleukin 2, and TNF-a 4–6 *These authors contributed equally to this work. J Cutan Pathol 2007: 34: 160–165 # 2006 The Authors Journal compilation # 2006 Blackwell Munksgaard doi: 10.1111/j.1600-0560.2006.00590.x Blackwell Munksgaard. Printed in Singapore Journal of Cutaneous Pathology 160