miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer.

The genes encoding microRNAs of the human miR-200 family map to fragile chromosomal regions and are frequently downregulated upon tumor progression. Although having been reported to regulate epithelial-to-mesenchymal transition and transforming growth factor-beta-driven cell invasion, the role of the miR-200 family in EGF-driven breast cancer cell invasion, viability, apoptosis and cell cycle progression is still unknown. In particular, there is no study comparing the roles of the two clusters of this miRNA family. In this study, we show for the first time that miR-200 family members differentially regulate EGF-driven invasion, viability, apoptosis and cell cycle progression of breast cancer cells. We showed that, all miR-200 family members regulate EGF-driven invasion, with the miR-200bc/429 cluster showing stronger effects than the miR-200a/141 cluster. Furthermore, expression of the miR-200a/141 cluster results in G1 arrest supported by increased p27/Kip1 and decreased cyclin dependent kinase 6 expression. In contrast, expression of the 200bc/429 cluster decreases G1 population and increases G2/M phase, in line with the observed reduction of p27/Kip1 and upregulation of the inhibitory phosphorylation of Cdc25C, respectively. To test the hypothesis that phenotypical differences observed between the two clusters are caused by differential targeting spectrums, we performed genome-wide microarray profiling in combination with gain-of-function studies. This identified phospholipase C gamma 1 (PLCG1), which was downregulated only by the miR-200bc/429 cluster, as a potential candidate contributing to these phenotypical differences. Luciferase reporter assays validated PLCG1 as a direct functional target of miR-200bc/429 cluster, but not of miR-200a/141 cluster. Finally, loss of PLCG1 in part mimicked the effect of miR-200bc/429 overexpression in viability, apoptosis and EGF-driven cell invasion of breast cancer cells. Our results suggest that the miR-200 family has a tumor-suppressor function by negatively regulating EGF-driven cell invasion, viability and cell cycle progression in breast cancer.

How does auxin enhance cell elongation? Roles of auxin-binding proteins and potassium channels in growth control.

Elongation growth and a several other phenomena in plant development are controlled by the plant hormone auxin. A number of recent discoveries shed light on one of the classical problems of plant physiology: the perception of the auxin signal. Two types of auxin receptors are currently known: the AFB/TIR family of F box proteins and ABP1. ABP1 appears to control membrane transport processes (H+ secretion, osmotic adjustment) while the TIR/AFBs have a role in auxin-induced gene expression. Models are proposed to explain how membrane transport (e.g., K+ and H+ fluxes) can act as a cross-linker for the control of more complex auxin responses such as the classical stimulation of cell elongation.

China marks World Population Day. Mr. Sven Burmester on China's population programme.

PIP: According to Sven Burmester, in an interview with China Population News, China is to be highly praised for its contribution to the stabilization of the world's population and sustainable development via its national family planning (FP) program. He said 300 million births had been averted according to estimates by the Chinese government; however, his calculation, which is based on the 1970 fertility level, is 800 million averted births. These achievements are important globally with regard to environmental protection. China has now attained the replacement level of its population and will achieve population stability by focusing on reproductive health and FP services, the empowerment of women, and international cooperation and exchange. Mr. Burmester said that economic development, government commitment, and public support are necessary to ensure continued success. He notes that some serious environmental problems that are barriers to sustainable development remain; the government is focusing on them, and the public is more aware of them.^ieng

Transcription and translation of the outer dense fiber gene (Odf1) during spermiogenesis in the rat. A study by in situ analyses and polysome fractionation.

Transcription and translation of the Odf1 gene encoding the major protein of sperm tail outer dense fibers has been investigated in rat spermatogenesis. Odf1 mRNA was detected by in situ hybridization from step 6 round spermatids up to step 17. The protein was detected immunohistochemically in the cytoplasm of step 7 spermatids up to step 18 and in the sperm tails. The distribution of Odf1 mRNA and the respective transcript sizes in polysomes and translationally inactive nonpolysomal ribonucleoprotein particles has been investigated by fractionation on sucrose gradients and Northern blot analysis of the isolated RNA. In adult rat testis about 30% of Odf1 mRNA is associated with the polysomal fraction, but the bulk is stored in translationally inactive ribonucleoprotein particles. In 35-day old rat testis, in which spermatids have reached step 15 of spermiogenesis, only about 10% of Odf1 mRNA can be found in the polysomal fraction. It seems therefore, that translation of Odf1 is greatly enhanced in the maturation phase of spermiogenesis during which a marked increase in diameter of outer dense fibers takes place. In the polysomal fraction, Odf1 transcripts are of heterogeneous size. Northern blot analysis of fractionated RNA digested with RHaseH revealed the presence of both Odf1 transcripts (Burfeind and Hoyer-Fender, 1991: Dev Biol 148: 195-204; Burfeind et al., 1993: Eur J Biochem 216: 497-505) on polysomes. While the larger transcript population is heterogeneous in size due to variable polyA-shortening, the smaller transcript population is not deadenylated compared to those present in nonpolysomal fractions.