Parathyroid hormone-related protein expression in gynecic squamous carcinoma cells

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Abstract
Background. The regulation of parathyroid hormone-related protein (PTH-rP) mRNA levels and immunoreactive (ir)PTH-rP formation by peptide growth tors, particularly transforming growth factor-β (TGF-β) and epidermal growth factor (EGF), in squamous cell carcinomas of gynecologic origin is largely unknown. Methods. PTH-rP mRNA levels were evaluated by Northern analysis in A431 cells (derived from a human vulvar epidermoid carcinoma) and ME-180 cells (derived from a human papillomavirus-infected squamous cell carcinoma of the cervix). PTH-rP protein levels in cell culture media were evaluated using both radioimmunoassay and immunoradiometric assay techniques. These results were compared with those from a lung carcinoid cell line known to produce PTH-rP, namely, NCI-H727 cells. Results. TGF-β1 or EGF treatment caused an increase in the levels of PTH-rP mRNA in A431 cells; these increases in PTH-rP mRNA were detectable after 60 minutes of treatment, were maximal at approximately 4-8 hours, and were approximately additive. Immunoreactive PTH-rP was not detectable (using two different PTH-rP immunoassays) in the culture medium or cell sonicates of A431 cells before or after treatment with TGF-β1, EGF, or TGF-βl plus EGF. ME-180 cells responded to EGF (but not to TGF-Bl) with an increase in the level of PTH-rP mRNA as early as 2 hours; irPTH-rP was present (by use of either immunoassay) in the medium of these cells at 8 and 24 hours. In NCI-H727 (human lung carcinoid) cells, TGF-β1 and E:GF acted alone and synergistically to effect increases in PTH-rP mRNA and the accumulation of irPTH-rP. Conclusions. TGF-β1 and EGF regulation of PTH-rP gene expression in squamous cell carcinomas of gynecologic origin is unique for each cell line studied and different from that in human lung carcinoid cells. Cancer 1994; 73:1515-21.

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