Natasha Kyprianou, Ph.D.
Laboratory of Prostate Tumorigenesis
The current research efforts in this laboratory are focused on studying the molecular changes involved in deregulation of the negative growth control mechanisms during prostate tumorigenesis. Apoptosis has been recognized as an important component of the homeostatic equilibrium during normal development and tissue maintenance. Recent kinetic studies have demonstrated that during the development of benign (BPH) and malignant growth of the prostate (prostate cancer) major changes occur in the rate of cell proliferation and the rate of apoptosis that result in a net increase in epithelial cell number, thus disrupting the growth equilibrium of the prostate gland. TGF-b has been shown to be a potent negative regulator of prostate growth via its ability to inhibit cell proliferation and to induce apoptosis. Recent evidence from our laboratory indicates that loss of expression of transforming growth factor-b receptor type II, an essential component of the signaling pathway that transduces the negative growth effects (antiproliferative and apoptotic) of TGF-b , occurs in prostate cancer and this loss correlates with tumor grade. This evidence highlights the significance of a dysfunctional TGF-b signaling pathway in prostate tumorigenesis. Genetic studies are being conducted to investigate the incidence of mutational changes of TGF-b receptor R-II, as well as the potential deregulation of downstream (post-receptor) effectors of the TGF-b signaling mechanisms, such as the Smad proteins, during prostate cancer progression.
An additional focus of this laboratory is the identification of key molecular determinants of the apoptotic cell death cascade as significant therapeutic targets for the effective treatment of both androgen-dependent and androgen-independent prostatic tumors.
We have demonstrated that androgen-independent human prostate cancer cells undergo apoptosis in response to ionizing irradiation and selected chemotherapeutic drugs. Our recent efforts are directed towards the development of combination strategies that will enhance radiosensitivity of prostate cancer cells, thus optimizing radiotherapy for advanced prostate cancer.
Recent PublicationsTu H, Jacobs SC, Borkowski A, Kyprianou N 1996 Incidence of apoptosis and cell proliferation in prostate cancer: Relationship with TGF-b and bcl-2 expression. Int J Cancer 69:357-363.
Kyprianou N, King ED, Bradbury D, Rhee J 1997 Bcl-2 overexpression delays radiation-induced apoptosis without affecting clonogenic survival in human prostate cancer cells. Int J Cancer 70:341-348.
Guo Y, Jacobs SC, Kyprianou N 1997 Down-regulation of protein and mRNA expression for TGF-b type I and type II receptor in human prostate cancer. Int J Cancer 71:573-579.
Kyprianou N 1997 Role of apoptosis in development of benign prostatic hyperplasia and prostate cancer: Clinical significance in diagnosis and treatment. Prostate: Basic and Clinical Aspects, Naz, R (ed) CRC Press, pp 181-199.
Guo Y, Kyprianou N 1997 Overexpression of TGF-b type II receptor in human prostate cancer cells LNCaP, restores TGF-b sensitivity and suppresses tumorigenic growth. Cell Growth and Differentiation, in press.
