Molecular insights into altered cell cycle regulation and genitourinary malignancy

Transforming growth factor-? and prostate cancer

“…Although other TGF~3 receptors (types IV-VI) and binding proteins have been identified, they TGF]31 has the fascinating ability to override the action of mitogens by inhibiting the cell in the G1 phase of the cell cycle, which prevents the cell's transition into the S phase (DNA synthesis) [2,19,33]. TGF[3 mediates its growth-inhibitory effects by regulating the complex interactions of tumor-suppressor genes (pRb and p53), cyclins, cyclin-dependent kinases, and protooncogenes (c-myc; reviewed in Steiner et al [65]). Disruption of this highly controlled TGF~I antiproliferative pathway may result in unrestrained cell growth [34].…”

“…of the TGF~31-signaling pathway is beyond the scope of this review (interested readers are referred to Steiner et al [65]) Briefly, however, Moses and associates [6,48,[52][53][54] have proposed a mechanism by which TGF~31 may mediate its inhibitory effects on cell proliferation (Fig.3). In murine and human keratinocytes, TGF~31 requires the retinoblastoma protein (pRb) to inhibit the transcription of protooncogene c-myc.…”