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 PNTIA and PNTIB. They retained the characteristics of prostatic epithelial cells, but did not clone in soft agarose. PNTIA occasionally formed undifferentiated adenocarcinoma tumors in nude mice, but only in the presence of matrigel. PNTIA and PNTIB 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 PNTIA displayed c‐myc 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 PNTIB. PNTIB 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.