pp60v- Induction of Cyclin D1 Requires Collaborative Interactions between the Extracellular Signal-regulated Kinase, p38, and Jun Kinase Pathways

Abstract

The cyclin D1 gene is overexpressed in breast tumors and encodes a regulatory subunit of cyclin-dependent kinases that phosphorylate the retinoblastoma protein.

Induction of p21WAF1/CIP1 and cyclin D1 expression by the Src oncoprotein in mouse fibroblasts: role of activated STAT3 signaling

“…Our ®ndings demonstrate that v-Src induces expression of the cyclin D1 promoter, consistent with the recent ®ndings of others (Lee et al, 1999). While the evidence suggests that STAT3 directly regulates the p21 promoter (Chin et al, 1996;Bellido et al, 1998), it remains to be determined whether STAT3 acts directly by binding to the cyclin D1 promoter or through an intermediate.…”

“…There is evidence that v-Src transformation results in altered expression of cyclins and CKIs, suggesting that Src may induce oncogenesis at least in part by modulating the expression of critical components of cell cycle regulation (Johnson et al, 1998a;Lee et al, 1999). Furthermore, other studies indicate that STATs regulate expression of the p21 WAF1/CIP1 and cyclin D genes (Chin et al, 1996;Matsumura et al, 1997;Bellido et al, 1998;Johnson et al, 1998b;Florenes et al, 1999;Wen et al, 1999).…”

Transgenic mouse models of human breast cancer

“…As with the c-myc transgenic models, the long latency and focal nature of these tumors suggests that although cyclin D1 can promote mammary tumorigenesis, additional genetic changes are needed for the development of overt mammary carcinomas. Consistent with this view, mammary epithelial expression of cyclin D1 has been implicated as an important event in mammary tumor induced by activated Src kinases, integrin linked kinase (ILK) and ErbB-2 (Lee et al, 1999(Lee et al, , 2000Radeva et al, 1997). Conversely germline inactivation of cyclin D1 results in impaired mammary epithelial gland development (Fantl et al, 1999).…”

Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

“…This suggests that a phosphoprotein involved in cell cycle control could be a speci®c substrate for RPTPa. v-Src is capable of inducing cyclin D1 in MCF7 cells (Lee et al, 1999). It is unclear to what extent c-Src activation by RPTPa is comparable to v-Src expression, and the arrest-inducing e ect of RPTPa may or may not be mediated through Src family kinases.…”