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Decreased Expression of Srcasm in Actinic Keratoses and Squamous Cell Carcinomas
Author(s) -
Dans Michael J.,
Elenitsas Rosalie,
Seykora John T.
Publication year - 2005
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/j.0303-6987.2005.320be.x
Subject(s) - fyn , keratinocyte , pathology , downregulation and upregulation , cancer research , immunohistochemistry , kinase , biology , medicine , cell culture , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , biochemistry , genetics , gene
Srcasm, a Src activating and signaling molecule, is a recently discovered substrate of the Src family kinase, Fyn. Although Srcasm can bind downstream signaling molecules, such as Grb2 and the p85 subunit of phosphoinositide 3‐kinase, the physiologic role of Srcasm is unknown. Because Fyn is believed to promote keratinocyte differentiation, we hypothesized that Srcasm may also promote keratinocyte differentiation and, thus, antagonize squamous cell carcinoma (SCC) formation. The purpose of this study, therefore, was to determine if Srcasm expression was decreased in SCC’s and actinic keratoses (AK). Using immunohistochemisty with a polyclonal affinity‐purified anti‐Srcasm antibody, we evaluated the expression of Srcasm in parafin imbedded sections of AK, SCC in‐situ (SCIS), and SCC from up to 15 different patients each. The expression of Srcasm in these lesions was compared to normal peri‐lesional skin of the same biopsy specimen or normal skin from separate biopsies. We found that Srcasm expression was decreased in approximately 50% of the AK and SCC‐IS samples and in over 90% of the SCC samples. This increased prevalence of Srcasm downregulation from pre‐malignant to less differentiated malignant lesions, supports our hypothesis that Srcasm, by functioning downstream of Fyn, may promote keratinocyte differentiation.