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The anterior gradient protein-2 (AGR2) is inducible by oestrogen and itself can induce metastasis in a rat model for breast cancer. Here, a rabbit antibody to recombinant human AGR2 was used to assess its prognostic significance in a retrospective cohort of 351 breast cancer patients treated by adjuvant hormonal therapy. The antibody stains 66% of breast carcinomas to varying degrees. The percentage of positive carcinoma cells in tumours directly correlates with the level of AGR2 mRNA (Spearman's rank correlation, P = 0.0007) and protein (linear regression analysis r2 = 0.95, P = 0.0002). There is a significant association of staining of carcinomas for AGR2 with oestrogen receptor alpha (ERalpha) staining and with low histological grade (both Fisher's Exact test P<0.0001). In the ERalpha-positive cases, but not the ERalpha-negative cases, when subdivided into the separate staining classes for AGR2, there is a significantly progressive decrease in patient survival with increased staining (log rank test, P = 0.006). The significant association of staining for AGR2 with patient death over a 10-year period (log rank test P = 0.007, hazard ratio = 3) only becomes significant at 6 years of follow-up. This may be due to the cessation of adjuvant hormonal therapy at an earlier time, resulting in adverse re-expression of the metastasis-inducing protein AGR2. [ABSTRACT FROM AUTHOR]

A metastatic phenotype can be induced in benign rat mammary cells (Rama 37 cells) by transfecting them with metastasis-inducing DNAs (Met-DNAs). Stable transfection of Met-DNAs increases the level of the metastasis-associated protein, osteopontin. Randomly picked clonal cell lines have been established from the pool of Rama 37 cells transfected with one metastasis-inducing DNA, C9-Met-DNA. In these cell lines, moderate correlation is observed between the copy number of C9-Met-DNA and their metastatic potential (linear regression coefficient, R2=0.48). A very close correlation is observed between the cell lines’ metastatic potential in vivo and the osteopontin mRNA levels in vitro (R2=0.74), but not with another metastasis-associated protein in this system, S100A4 (R2=0.21). A close correlation is also observed between osteopontin mRNA levels and the adhesive potential (R2=0.91) of the cells, but not with their growth rate in vitro (R2=0.03). These observations support the previous suggestion that osteopontin is the direct effector of C9-Met-DNA and that the presence of C9-Met-DNA is necessary, if not sufficient, for the induction of metastasis in vivo in this system. Additionally, these results suggest that Rama 37 cells with increased osteopontin mRNA levels become metastatic not through an increased growth rate, but through an increase in cellular adhesiveness.British Journal of Cancer (2004) 90, 1796-1802. doi:10.1038/sj.bjc.6601683 www.bjcancer.com Published online 27 April 2004 [ABSTRACT FROM AUTHOR]

A suppression subtraction cDNA library representing mRNAs expressed at a higher level in a benign breast tumour-derived cell line relative to the malignant MCF-7A cell line contained cDNAs corresponding to mRNAs for plasminogen activator inhibitor I, annexin VIII and the EF-hand protein S100A2. S100A2 protein has previously been shown to be expressed in normal human breast epithelium, but not in human breast carcinoma cell lines. Using a PCR-based assay and in situ hybridization on histological sections of human breast specimens, the mRNA for S100A2 was shown to be present in all benign breast lesions examined as well as in normal epithelium. S100A2 mRNA was detectable in 37% of specimens of carcinoma in situ, but in less than 15% of carcinoma specimens. The results suggest that the loss of S100A2 is associated with the development of malignant cells and is not associated with early tumour development. [ABSTRACT FROM AUTHOR]

The article discusses stem cells in rat mammary development and cancer. A number of mammotrophic hormones have been identified in mice and rats from a series of endocrine gland ablation and hormone replacement experiments. These same hormones are required for the growth of dimethylbenz[a]anthracene-induced rat mammary tumors. These include prolactin, growth hormone and estrogens.

We have devised a simplified method for the purification of the bacterial initiator tRNA, tRNAfMet in amounts greater than 100 mg from 10 g of unfractionated tRNA. The purification of the normal methionine tRNA, tRNAmMet, was also achieved but with a lower yield. During the fractionation studies we identified two chromatographically separable species of tRNAfMet and two of tRNAmMet. The triplet binding assay did not differentiate between fMet-tRNAf1 and fMet-tRNAr2 or between Met-tRNAm1 and Met-tRNAm2. An anticodon containing fragment of tRNAmMet did not inhibit the charging of tRNAfMet or of tRNAmMet under conditions where it should behave as a linear sequence of nucleotides. Both tRNAfMet and tRNAmMet contain approximately one mole of £he minor nucleoside, 4-thiouridine, per mole of tRNA. In our functional tests the presence of 4-thiouridine was not necessary for the biological activity of tRNAfMet. [ABSTRACT FROM AUTHOR]