At least six mutations in the CDKN1C
gene have been found to cause this condition .
Mutations in the PCNA-binding domain of CDKN1C
cause IMAGe syndrome.
ZAC, LIT1 (KCNQ1OT1) and [p57.sup.KIP2] (CDKN1C
) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome.
(120,121) Partial methylation of the CDKN1C/p57KIP2 promoter CpG islands in IPMNs and pancreatic cancer cell lines was correlated with a corresponding decrease in CDKN1C
Clark, "Cell cycle genes PEDF and CDKN1C
in growing deer antlers," Anatomical Record, vol.
Our results show that, in MCF-7 cells, MAA alone was able to decrease the steady-state mRNA levels of ER[alpha] (1.9-fold decrease) and the estrogen-responsive genes pS2 (1.6-fold), MYC (1.5-fold), and SPUVE (2.7-fold) compared with vehicle controls (Figures 2B and 3A), whereas it increased the expression of CDKN1C
(4.2-fold increase), a gene that was modestly down-regulated by [E.sub.2] in our experiments (data not shown).
(14) The most commonly involved genes are CDKN1C
([p57.sup.KIP2]), H19, IGF-II, and KVLQT.
Based on their structure and CDK specificity, CDKIs are classified into the INK4 family CDKIs ([p16.sup.INK4a] (Cdkn2a), [p15.sup.INK4b] (Cdkn2b), [p18.sup.INK4c] (Cdkn2c), and [p19.sup.INK4d] (Cdkn2d)) that inhibit CDK4/6 activity by competing with cyclin D to bind CDK4/6 and the Cip/Kip family CDKIs ([p21.sup.Cip1] (Cdkn1a), [p27.sup.Kip1] (Cdkn1b), and [p57.sup.Kip2] (Cdkn1c
)) that associate with both cyclins and CDKs and interfere with the activities of cyclin D-, E-, A-, and B-CDK complexes.