Hedgehog signaling regulates proliferation of prostate cancer cells via stathmin1.
Hedgehog (Hh) signaling is an essential pathway in embryonic development of prostate. Hh also plays roles in the proliferation of progenitor cells and cancer cells of adult prostate. However, how Hh signaling contributes to carcinogenesis of prostate is poorly understood. Stathmin1 is a microtubule-regulating protein that plays an important role in the assembly and disassembly of the mitotic spindle. Stathmin1 is expressed in normal developing mouse prostate and in prostate cancer. The expression pattern of stathmin1 is similar to that of Shh in prostate development and cancer, suggesting a connection between these two proteins. In this study, we examined the relationship between stathmin1 and Hh signaling. Here, we show that stathmin1 expression is regulated by Hh signaling in prostate cancer cells. Cyclopamine, a specific inhibitor of Hh signaling, reduced the expression of stathmin1 in prostate cancer cells. However, the Shh peptide induced stathmin1 expression. Overexpression of Gli1 further confirmed the relationship. Co-expression of stathmin1 and Patched 1, a receptor for Hh signaling was observed in prostate cancer tissues. Cyclopamine and stathmin1 siRNA both decreased proliferation of prostate cancer cells but did not produce an additive effect, suggesting a common pathway. These results suggest that Hh signaling regulates proliferation of prostate cancer cells by controlling stathmin1 expression.
Chung
Moon-Kee
MK
Department of Urology, Pusan National University, Mulgeum-Eup, Beomeo-Ri, Yangsan, 626-870, South Korea.
Kim
Hyun-Jung
HJ
Lee
Young-Suk
YS
Han
Myoung-Eun
ME
Yoon
Sik
S
Baek
Sun-Yong
SY
Kim
Bong-Seon
BS
Kim
Jae-Bong
JB
Oh
Sae-Ock
SO
D000818:Animals; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020868:Gene Silencing; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011471:Prostatic Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015398:Signal Transduction; D050777:Stathmin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014704:Veratrum Alkaloids / Q000494:pharmacology
D004791:Enzyme Inhibitors; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C493995:STMN1 protein, human; D050777:Stathmin; D014704:Veratrum Alkaloids; C000541:cyclopamine