Coexpression of adult T-cell leukemia-derived factor, a human thioredoxin homologue, and human papillomavirus DNA in neoplastic cervical squamous epithelium

Abstract

Adult T‐cell leukemia‐derived factor (ADF) is an autocrine interleukin‐2 receptor‐inducing factor produced by human T‐lymphotropic virus‐1 (HTLV‐1)‐transformed lymphocytes, which has a high structural homology with an endogenous dithiol reducing coenzyme, thioredoxin. Its localization was investigated immunohistochemically in the cervix, using normal tissue (27 samples) and squamous neoplastic tissue (three condylomas, 42 cervical intraepithelial neoplasia [CIN] samples, 34 invasive squamous cell carcinoma samples). The expression of human papillomavirus (HPV) DNA was also studied in serial sections of the same subjects. Normal squamous cells and glandular cells of the cervix were negative for ADF. However, intracytoplasmic and/or intranuclear ADF‐positive cells were usually found in the intermediate and superficial layers of the neoplastic squamous epithelium of condylomas (three of three cases) and CIN (35/42 cases). HPV DNA was detected in all condylomas and in 27 of 42 CIN specimens. HPV DNA‐positive cells were usually localized in the intermediate and superficial layers of the neoplastic squamous epithelium. These HPV DNA‐positive cells were also positive for ADF. Invasive squamous cell carcinoma was also positive for ADF (24/34 cases) and HPV DNA (11/34 cases). The coexpression of HPV DNA and ADF was observed in all HPV DNA‐positive cases. Coexistence of HPV DNA and ADF immunopositivity in neoplastic squamous cells of the cervix suggests that ADF expression closely reflects the intracellular event on HPV DNA replication.

Identification of Thioredoxin-binding Protein-2/Vitamin D3 Up-regulated Protein 1 as a Negative Regulator of Thioredoxin Function and Expression

“…Human TRX was discovered as adult T-cell leukemia-derived factor from human T-cell lymphotropic virus-I transformed T-cells (9). Elevated levels of TRX expression has been observed in some human tumors (51,52). In addition, TRX transfected cells exhibited severalfold increased colony formation in soft agarose, whereas a redox-inactive mutant TRX C32S/C35S acts in a dominant negative manner to inhibit proliferation (53).…”

Molecular pharmacology and antitumor activity of palmarumycin-based inhibitors of thioredoxin reductase

“…Thioredoxin-1 is overexpressed in many human tumors (14)(15)(16)(17) where it is associated with increased cell proliferation, decreased apoptosis (18), and decreased patient survival (19,20). The redox activity of thioredoxin-1 is necessary for its biological effects in stimulating cancer cell growth and inhibiting apoptosis (12,13,34).…”

Redox control of resistance to cis-diamminedichloroplatinum (II) (CDDP): protective effect of human thioredoxin against CDDP-induced cytotoxicity.

“…hTRX has been shown to be highly expressed in a variety of human malignant cells, including adult T cell leukemia caused by human T cell lymphotropic virus-I, squamous cell carcinoma of the uterine cervix, hepatocellular carcinoma, lung carcinoma, and adenocarcinoma of the gastrointestinal tract (6,(20)(21)(22). In addition, it has been recently recognized that some CDDP-resistant human cancer cell lines have higher levels of hTRX expression (23,24).…”