Overexpression of TC-PTP in murine epidermis attenuates skin tumor formation

T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, has been shown to function as a tumor suppressor during skin carcinogenesis. In the current study, we generated a novel epidermal-specific TC-PTP-overexpressing (K5HA.Ptpn2) mouse model to show that TC-PTP contributes to the attenuation of chemically induced skin carcinogenesis through the synergistic regulation of STAT1, STAT3, STAT5, and PI3K/AKT signaling. We found overexpression of TC-PTP increased epidermal sensitivity to DMBA-induced apoptosis and it decreased TPA-mediated hyperproliferation, coinciding with reduced epidermal thickness. Inhibition of STAT1, STAT3, STAT5, or AKT reversed the effects of TC-PTP overexpression on epidermal survival and proliferation. Mice overexpressing TC-PTP in the epidermis developed significantly reduced numbers of tumors during skin carcinogenesis and presented a prolonged latency of tumor initiation. Examination of human papillomas and squamous cell carcinomas (SCCs) revealed that TC-PTP expression was significantly reduced and TC-PTP expression was inversely correlated with the increased grade of SCCs. Our findings demonstrate that TC-PTP is a potential therapeutic target for the prevention of human skin cancer given that it is a major negative regulator of oncogenic signaling

PRESENCE OF HPV TYPE 6 IN DYSPLASIA AND CARCINOMA ARISING FROM RECURRENT RESPIRATORY PAPILLOMATOSIS

Background. We collected rare cases of recurrent respiratory papillomatosis (RRP) undergoing malignant transformation. We sought to identify human papillomavirus (HPV) subtypes in areas of papilloma, dysplasia, and carcinoma and investigate thve pattern of protein overexpression. Methods. Three patients whose disease underwent malignant transformation from RRP to carcinoma were subjected to this study, Morphologically distinct areas in the pathology specimen of each patient were diagnosed as papilloma, dysplasia. and carcinoma. Each lesion was separately obtained by laser capture microdissection and was PCR amplified for the presence of HPV. A DNA chip was used to determine the type of HPV in each area. Immunohistochemistry for p53, Ki-67, and pRb was performed. Results. HPV type 6 was present in all specimens tested positive, Expression of p53 and Ki-67 increased with increasing severity of dysplastic change. Conclusion. Although HPV type 11 is most frequently associated with malignant change of RRP. HPV type 6 may also contribute to play an equally important role in RRP carcinogenesis. (C) 2008 Wiley Periodicals, Inc. Head Neck 31: 1095-1101, 2009Gerein V, 2005, OTOLARYNG HEAD NECK, V132, P392, DOI 10.1016/j.otohns.2004.09.025FEHRMANN F, 2005, METHOD MOL BIOL, V292, P317Reidy PM, 2004, LARYNGOSCOPE, V114, P1906, DOI 10.1097/01.mlg.0000147918.81733.49Lee SA, 2003, CANCER LETT, V198, P187, DOI 10.1016/S0304-3835(03)00312-4Go C, 2003, ANN OTO RHINOL LARYN, V112, P298Lele SM, 2002, ARCH PATHOL LAB MED, V126, P1184Dedo HH, 2001, LARYNGOSCOPE, V111, P1639Gupta D, 2001, APPL IMMUNOHISTO M M, V9, P86HARTNICK CJ, 2001, CURR OPIN OTOLARYNGO, V9, P374Venuti A, 2000, J MED VIROL, V60, P396Stern Y, 2000, OTOLARYNG HEAD NECK, V122, P378Moore CE, 1999, OTOLARYNG HEAD NECK, V120, P698Rady PL, 1998, LARYNGOSCOPE, V108, P735Lin KY, 1997, LARYNGOSCOPE, V107, P942Klozar J, 1997, ACTA OTO-LARYNGOL, P100Lie ES, 1996, ACTA OTO-LARYNGOL, V116, P900Sakakura A, 1996, J LARYNGOL OTOL, V110, P75HAVRE PA, 1995, CANCER RES, V55, P4420POU AM, 1995, ANN OTO RHINOL LARYN, V104, P758DOYLE DJ, 1994, ARCH OTOLARYNGOL, V120, P1273GUILLOU L, 1991, AM J SURG PATHOL, V15, P891GERDES J, 1991, AM J PATHOL, V138, P867LINDEBERG H, 1989, ACTA OTO-LARYNGOL, V107, P141ZAROD AP, 1988, J CLIN PATHOL, V41, P280BYRNE JC, 1987, NEW ENGL J MED, V317, P873