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Estradiol Inhibits Growth of Hormone-nonresponsive PC3 Human Prostate Cancer Cells¹

Hormone Biochemistry Laboratories, Medical School, University of Palermo, Via Marchese Ugo 56, 90141 Palermo [G. C., E. F., L. C.]; Experimental Oncology and Molecular Endocrinology Units, Palermo Branch of National Institute for Cancer Research of Genoa, c/o "M. Ascoli" Cancer Hospital Centre, Palermo [M. L. C., L. C.]; Institute of Biology and Genetics, University of Genoa [D. A. C., E. D'A.]; and Laboratory of Molecular Biology, National Institute for Cancer Research, Genoa [U. P., G. V.], Italy

Significant inhibition of proliferative activity in PC3 human prostate cancer cells by estradiol is reported, accompanied by experimental evidence for a specific estrogen receptor (ER). Radioligand-binding assays revealed the presence of high affinity sites of estrogen binding in the nuclear compartment of PC3 cells. In addition, using a reverse transcriptase-polymerase chain reaction system, we obtained evidence of either normal or a variant ER mRNA; the latter, which lacks the entire exon 4, is coexpressed with normal ER mRNA and has been recently characterized in our laboratories. The likelihood that the inhibitory effect exerted by estradiol could be mediated by an increase of transforming growth factor ß (TGFß) production was also investigated. Use of monoclonal antibodies against TGFß₁ produced a 3-fold increase of growth rate in PC3 cells; this clearly speaks for high levels of endogenous TGFß₁. This effect was almost completely abolished after addition of 100 nM estradiol. However, we failed to demonstrate any increase of TGFß₁ mRNA after estradiol administration using Northern blot analysis. Further studies are needed to ascertain whether the estradiol-induced growth inhibition of PC3 cells is either mediated by other TGFß species or exerted via alternative mechanism(s).

¹ Partly supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) and the Consiglio Nazionale delle Ricerche, Special Project "Aging" (c.n. 93.435.PF40).

² To whom requests for reprints should be addressed, at Hormone Biochemistry Laboratories, University of Palermo, Via Marchese Ugo 56, 90141 Palermo, Italy.

Received 9/ 7/93. Accepted 12/29/93.

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