In search for nuclear proteins that interact with the human thymidine kinase (htk) promoter, we discovered that p37AUF, a hnRNP C-like protein, and hnRNP A1, both members of the heterogeneous ribonucleoprotein family, can bind with high affinity to an ATTT sequence motif contained within the cell cycle regulatory unit (CCRU). We report here that over-expression of p37AUF stimulates gene expression mediated by the htk promoter in a promoter-sequence specific manner, whereas hnRNP A1 suppresses it. Both recombinant p37AUF and hnRNP A1 can bind the htk CCRU, suggesting that their binding to the DNA target does not require additional cellular components. We further discovered that hnRNP K is a potent suppressor of htk mediated gene activity. However, its mechanism of action is mediated through protein-protein interaction, since hnRNP K itself cannot bind the htk CCRU but can competitively inhibit the binding of other hnRNPs. The binding site for the hnRNPs on the htk CCRU is not required for S-phase induction of the htk promoter. However, in stable but not transient transfectants, the mutation of the hnRNP binding site results in 5- to 10-fold reduction of htk mediated gene activity in synchronized and exponentially growing cells. Collectively, these findings support emerging evidence that hnRNPs, in addition to their traditional role in RNA biogenesis, could be regulators of gene expression through direct DNA binding or interaction with other proteins.

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Background Controversy exists in the literature regarding the optimal site for lymphatic mapping in breast cancer. This study was designed to characterize lymphatic drainage patterns within the same patient after subareolar (SA) and peritumoral (PT) radiopharmaceutical injections and examine the impact of reader interpretation on reported drainage. Methods In this prospective trial, 27 women with breast cancer underwent sequential preoperative SA and PT injections of 0.5 to 2.7 mCi of technetium-99 m filtered sulfur colloid 3 days or more apart. Patterns of radiopharmaceutical uptake were reviewed independently by two nuclear medicine physicians. Inter-reader agreement and injection success were assessed in conjunction with observed drainage patterns. Results There was near perfect inter-reader agreement observed on identification of axillary LN drainage after PT injection (P = 0.0004) and substantial agreement with SA injection (P = 0.0344). SA injection was more likely to drain to only axillary LNs, whereas PT injection appeared more likely to drain to both axillary and extra-axillary LNs, although no statistically significant differences were found. All patients with extra-axillary drainage after PT injection (n = 6 patients) had only axillary drainage after SA injection. Dual drainage was observed for six patients with PT injection and one patient with SA injection. Conclusions Our findings suggest that radiopharmaceutical injected in the SA location has a high propensity to drain to axillary LNs only. After controlling for patient factors and demonstrating inter-reader agreement, the inability to demonstrate statistically significant differences in drainage based on injection site suggests that lymphatic drainage patterns may be a function of patient and tumorspecific features.