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Tumorigenicity of SV40 T antigen immortalized human prostate epithelial cells: Association with decreased epidermal growth factor receptor (EGFR) expression
Author(s) -
Bae Victoria L.,
JacksonCook Colleen K.,
Brothman Arthur R.,
Maygardens Susan J.,
Ware Joy L.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580517
Subject(s) - biology , epidermal growth factor , epidermal growth factor receptor , cytokine , cell culture , tgf alpha , prostate , cancer research , antigen , growth factor , antibody , transforming growth factor , transfection , tumor progression , medicine , microbiology and biotechnology , endocrinology , receptor , cancer , immunology , biochemistry , genetics
Our primary objectives were to: 1) develop a system for the study of prostatic tumor evolution; and 2) examine the role of the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) pathway in prostate tumor progression. Adult human prostate epithelial cells previously immortalized by transfection with the SV40 T antigen gene (P69SV40T) produced tumors in only 2/18 mice with a 6 month latency period. Reinjection of cells recovered from these tumors after 1 or 2 cycles of growth in nude mice produced tumors in 2/4 and 2/3 mice with markedly decreased latent intervals of 12, 25, 25 and 25 days each. The chromosomal complement of each tumor was human, consistently pseudodiploid, and retained the Y chromosome. In both anchorage‐independent and adherent cell growth assays, EGF stimulated proliferation by approximately 2‐fold in both the parental P69SV40T line and the tumor sublines. The tumor sublines expressed less EGFR protein than the parental line, as assessed by Western immunoblotting and flow cytometric analysis. Immunoprecipitation revealed increased production of the 18 and 25 kDa TGF‐α precursors parallel to decreases in detectable EGFR. The growth of both the parental P69SV40T line and the tumor sublines was inhibited by a neutralizing antibody to TGF‐α under serum‐free defined conditions. Inclusion of the TGF‐α neutralizing antibody consistently inhibited the proliferation of the tumor sublines more than P69SV40T in both proliferation and [ 3 H]thymidine incorporation assays. This finding suggests that the increased tumorigenicity and decreased latent interval observed among the human prostate tumor cells is partially due to activation of the TGF‐α/EGFR autocrine network.