Growth regulation of hormonal cancer

​Description of Research

Our group has worked on growth regulation of hormonal cancer. We have particularly studied the autocrine/paracrine mechanisms mediated by the fibroblast growth factor (FGF)/FGF receptor (FGFR) pathways in breast and prostate cancer growth, invasion and metastasis. We have used cell lines, tissue cultures and gene-modulated mouse lines as experimental models to study hormone and FGFR signaling in epithelial-mesenchymal interactions in prostate carcinogenesis, breast and prostate cancer cell proliferation and in bone marrow cell – breast cancer cell interactions as a  model for bone metastasis.  We have also used explant cultures to study the hormone and hormonal drug compound regulation of normal and malignant human mammary tissue obtained from reduction mammoplasties and breast cancer surgery.  Recently, we have also focused on the analysis of human prostate cancer specimens collected from total prostatectomies. Using tumor tissue microarrays and fresh tissue samples we have studied the role of previously poorly characterized members of FGF/FGFR signaling, including FGF13 and FGFR5.  We have also established and analyzed patient-derived prostate cancer xenografts (PDX) of tumor tissue specimens from total prostatectomies. Using intratibial implantation of PDX tissues we have succeeded in developing models of prostate cancer bone metastasis. These models are being used to test drug sensitivity of prostate cancer tissues, including responsiveness to clinically used drugs as well as to investigational drug compounds such as novel FGFR inhibitors.

List of Personnel

Natalija Eigéliené, MD, PhD, researcher
Soili Jussila, technician
Tiina Kähkönen, MSc, PhD student
Yu Lan, MD, PhD student
Arttu Mäntylä, BSc, student
Miikka Tuomala, med. student
Mervi Toriseva, PhD, postdoctoral researcher

In collaboration with:
Matthias Nees, PhD, docent and his group
Johanna Tuomela, PhD, docent and her group
Maija Valta, MD, PhD, specialist in internal medicine

Selected Publications

Elo, T.D., Valve, E.M., Seppänen, J.A., Vuorikoski, H., Mäkelä, S.M., Poutanen, M., Kujala, P.M., Härkönen, P.L.: Fibroblast growth factor 8b (FGF-8b) –induced stromal activation is associated with development of mixed mPIN, adenocarcinoma and sarcoma lesions in the prostate of transgenic mice. Neoplasia 12 (11) 915-27, 2010

Nilsson, E.M., Brokken, L.J.S., Narvi, E., Kallio, M., Härkönen, P.L.: Identification of novel FGF8b target genes associated with regulation of cell cycle and proliferation in breast cancer cells. Mol Cell Endocrinol 6;358(1):104-15, 2012

Eigèlienè, N., Hurme, S., Erkkola, R., Härkönen, P.: Androgens inhibit the stimulatory action of 17β-estradiol in human breast in tissue culture J Clin Endocrinol Metab 97(7):E1116-27, 2012

Semenas J., Hedblom A., Sarwar M., Miftakhova R., Larsson R., Shcherbina L., Johansson M., Söderlind A., Härkönen P., Sterner O., Liao Persson J.: Novel role of PI3K/Akt-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci USA 2;111(35):E3689-98, 2014

Elo, T., Yu, L., Valve, E., Mäkelä, S., Härkönen, P.: Deficiency of ER beta and prostate tumorigenesis in FGF8b transgenic mice. Endocr Rel Cancer 21(4):677-90, 2014