Recurrent cytogenetic alterations of prostate carcinoma and amplification of c-myc or epidermal growth factor receptor in subclones of immortalized PNT1 human prostate epithelial cell line.

ABSTRACT

To develop an experimental prostate cancer model, we immortalized normal human prostate adult epithelial cells with SV40 large-T antigen. Two sublines were derived in culture, namely PNT1A and PNT1B. They retained the characteristics of prostate epithelial cells, but did not clone in soft agarose. PNT1A occasionally formed undifferentiated adenocarcinoma tumors in nude mice, but only in the presence of matrigel. PNT1A and PNT1B displayed common cytogenetic alterations a 10q arm deletion, which is a recurrent alteration in prostate carcinoma, chromosome losses and a translocation involving chromosome 5. An extensive study of oncogenic alterations occurring in these cells showed that PNT1A displayed c-myc gene amplification, forming an hsr on chromosome 4, as well as gene amplification, forming an hsr on chromosome 4, as well as c-myc mRNA overexpression, with a faster doubling time (25 hr); moreover, it seemed less sensitive to EGF than PNT1B. PNT1B had a doubling time identical to that of normal cells (48 hr) but displayed EGF receptor gene amplification accompanied by an increased number of EGF binding sites and sensitivity to EGF. Because both cell lines displayed cytogenetic and oncogenic alterations found in prostate cancer, as well as differing malignant potentials, they represent an interesting model for studying the progression of prostate tumors.