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Experimental analysis of the modulation of the transcription factor AP-2 expression in neuroectodermal cell lineages during the differentiation of microglial cells, cerebellar neurons and astrocytes in mouse brain shows that AP-2 expression contributes to the proliferation of astrocytic cell lineages and neurons, itself undergoing a cell type-specific modulation. The induction of AP-2 transcripts and protein during P19 cell-, astrocyte- and neuronal differentiation indicates that AP-2 functions as a retinoic acid-dependent regulator of the differentiation. AP-2 also mediates gene transcription in astrocytes and neurons, and protein kinase A inhibitors suppress the cAMP-based introduction of AP-2 expression during differentiation.

p27Kip1 and p21Cip1 are cyclin dependent kinase inhibitors which can arrest cell proliferation and p27 is a tumor suppressor gene. To address the mechanism of tumor suppression by p27 and to determine if p21 has a tumor suppressor phenotype, we utilized the two stage skin carcinogenesis model on p27 and p21 knockout mice. In this model, initiation, which involves mutation of H-ras induced by DMBA, can be distinguished from promotion induced by TPA, and progression to carcinoma. The mean number of papillomas did not differ between p27-/- and control littermates, but papilloma growth rate was increased and carcinomas developed earlier. Thus, p27 deficiency did not enhance initiation, but resulted in more rapid clonal expansion of initiated cells during promotion. TPA treatment reduced p27 expression in keratinocytes also supporting a role for p27 during promotion. Tumors from p27-/- mice contained mutant H-ras indicating that p27 deficiency did not substitute for mutant ras and further, that during ras driven tumor growth, p27 is partially antagonistic since its removal led to faster growth. The treated p27-/- mice also developed intestinal adenomas. p21-/- mice did not display a significant increase in tumor numbers, growth rate or progression to carcinomas and these tumors also had mutated H-ras. Carcinomas from p21-/- mice were more poorly differentiated with a high frequency of anaplastic spindle cell carcinomas. Thus p21 deficiency mainly resulted in higher grade undifferentiated tumors. [ABSTRACT FROM AUTHOR]

This article focuses on the murine genes. Activation of cyclin-dependent kinase-2 (cdk2) by cyclin E is a key event in driving cells from G 1 into S phase of the cell cycle. Cdkn lb, also known as p27 belongs to the Kip/Cip family of cdk inhibitors and responds to extracellular signals such as TGFB and cell contact by binding to cyclin Etc dk2 complexes. cyclin DIcdk4I6 and cyclin AIcdk2 complexes. Quiescent cells generally express higher levels of Cdkn lb than proliferating cells, and enforced expression of Cdkn1b inhibits cell proliferation.