Reported use of reporting guidelines among JNCI: Journal of the National Cancer Institute authors, editorial outcomes, and reviewer ratings related to adherence to guidelines and clarity of presentation.

BACKGROUND: Associations were examined between author-reported uses of reporting guidelines to prepare JNCI: Journal of the National Cancer Institute (JNCI) submissions, editorial decisions, and reviewer ratings for adherence to reporting guidelines and clarity of presentation. METHODS: At submission, authors were asked if they used reporting guidelines to prepare their manuscript and, if so, which one(s). Reviewers rated adherence to reporting guidelines and clarity of presentation. Data were gathered using a customized Editorial Manager Enterprise Analytics Report for submissions with first or final decisions that were submitted between November 1, 2015, and April 30, 2017. Manuscript types that would benefit from the use of reporting guidelines were included. All reviews were included in the analyses. Numerical values were given to each answer (yes, 1; no, 0) or reviewer rating (not applicable, 0; fair, 1; poor, 2; good, 3; very good, 4; and outstanding, 5), and scores were compared using two-sided t tests. RESULTS: Of 2209 submissions included in the analysis, 1144 (51.8%) indicated that at least one reporting guideline was used. The STROBE guidelines were the most common (n = 531, 24.0%). Of the 2068 (93.6%) submissions that were rejected, 1105 (50.1%) indicated using reporting guidelines and 963 (43.6%) did not (mean [SD] scores of rejected vs not rejected, 0.53 [0.50] vs 0.49 [0.50], P = .47). Of the 1033 ratings for adherence to reporting guidelines, mean (SD) scores for not rejected vs rejected submissions were 3.2 (1.61) vs 2.9 (1.57) (P = .005), and mean (SD) scores for reporting guidelines use vs no use were 3.1 (1.48) vs 2.9 (1.70) (P = .01). Of the 1036 ratings for clarity of presentation, mean (SD) scores for not rejected vs rejected submissions were 3.6 (1.00) vs 3.1 (1.08) (P < .001), whereas mean (SD) scores for reporting guidelines use vs no use were 3.3 (1.04) vs 3.3 (1.10) (P = .64). CONCLUSIONS: Among these JNCI submissions, reporting the use of reporting guidelines was not associated with editorial decisions or with reviewer ratings for clarity of presentation. Reviewer ratings for adherence to guidelines and clarity of presentation were associated with editorial decisions after peer review, and ratings for adherence to guidelines were associated with reported use of reporting guidelines.

Progesterone receptor deficient in chromatin binding has an altered cellular state.

Our previous work has shown that the progesterone receptor (PR) can exist in two distinct functional states in mammary adenocarcinoma cells. The differences in function included the ability to activate a promoter in organized chromatin, sensitivity to ligand, and ligand-independent activation. To determine whether these functional differences were because of altered cellular processing, we carried out biochemical analyses of the functionally distinct PRs. Although the majority of PR is localized to the nucleus, biochemical partitioning resulted in a loosely bound (cytosolic) fraction, and a tightly bound (nuclear) fraction. In the absence of progestins, the functionally distinct PRs differed significantly in partitioning between the two fractions. To characterize these fractions further, we analyzed interactions of unliganded PR with chaperones by coimmunoprecipitation. We determined that PR in the cytosolic fraction associated with hsp90 and p23. In contrast, PR in the nuclear fraction consisted of complexes containing hsp90, p23, and FKBP51 as well as PR that was dimerized and highly phosphorylated. Hormone treatment significantly reduced the formation of all PR-chaperone complexes. The hsp90 inhibitor, geldanamycin, similarly blocked transcriptional activity of both functionally distinct receptors. However, the two forms of the PR differed in their ability to associate with the mouse mammary tumor virus promoter in organized chromatin. These findings provide new information about the composition and distribution of mature progesterone receptor complexes in mammary adenocarcinoma cells, and suggest that differences in receptor subcellular distribution have a significant impact on their function. These findings also reveal that transiently expressed steroid receptors may not always be processed like their endogenous counterparts.

Rb localization and phosphorylation kinetics correlate with the cellular phenotype of cultured breast adenocarcinoma cells.

Retinoblastoma protein (Rb) expression has been correlated with state of differentiation, proliferation rate, and metastatic potential in breast adenocarcinomas and established cell lines. These observations, based on immunoreactivity of total Rb rather than hypophosphorylated protein, do not address the relationship between functional Rb and indicators of an aggressive transformed cellular phenotype. We hypothesized that the distribution of functional Rb and the kinetics of Rb phosphorylation would differ between cell lines representing immortalized mammary epithelium (MCF10A), differentiated nonmetastatic mammary adenocarcinoma (MCF-7), and poorly differentiated, highly metastatic mammary adenocarcinoma (MDA-MB-231) and that these differences would be informative of the cellular phenotype. Direct immunofluorescence microscopy was used to compare qualitatively the subcellular localization of total and hypophosphorylated Rb protein in synchronized and asynchronous cells. This technique was also used to quantitatively assess the amounts of hypophosphorylated Rb throughout the cell cycle in these representative cell lines. Total Rb stained more prominently than hypophosphorylated Rb in the nucleus of all asynchronous cells. Rb phosphorylation was more rapid in MCF-7 cells than in MCF10A cells, whereas Rb dephosphorylation appeared deregulated in MDA-MB-231 cells. We conclude that assessment of hypophosphorylated Rb may be more useful than assessment of total Rb for the evaluation of transformed breast adenocarcinoma phenotypes.

Retinoblastoma function is a better indicator of cellular phenotype in cultured breast adenocarcinoma cells than retinoblastoma expression.

Loss of or lowered retinoblastoma (Rb) expression has been included as a prognostic indicator in breast cancer. Low or no Rb expression is seen most commonly in high-grade breast adenocarcinomas, suggesting that a relationship may exist between loss of Rb and a less differentiated state, high proliferation rate, and high metastatic potential. In this study, we compared Rb function in two established breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, and in an established immortalized mammary epithelial cell line, MCF10A. Cells were synchronized in G0/G1 and were released for several durations, at which time total Rb protein, mRNA, and Rb/E2F/DNA complex formation were evaluated. Rb protein was significantly higher in the tumor cells than in MCF10A cells. However, Rb function was high for a longer duration in MCF10A cells as compared with MCF-7 and MDA-MB-231 cells. Our data support the general conclusion that Rb function, but not necessarily Rb protein, is lower in highly malignant breast adenocarcinoma cells as compared with lower grade tumor cells. These results emphasize the relevance of assessing Rb function over Rb protein. This is particularly important if Rb is to be used as a prognostic indicator for breast adenocarcinoma.