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J Macoska

Publications and source records attributed to J Macoska.

5 recordsLinked to original sources
PubMed1994

Alterations in cellular gene expression without changes in nuclear matrix protein content.

Cell metabolism and function are modulated in part by cell and nuclear shape. Nuclear shape is controlled by the nuclear matrix, the RNA-protein skeleton of the nucleus, and its interactions with cytoskeletal systems such as intermediate filaments and actin microfilaments. The nuclear matrix plays an important role in cell function and gene expression because active genes are bound to the nuclear matrix whereas inactive genes are not. It is unknown, however, how genes move on and off the matrix, and whether these events require compositional protein changes, i.e., alterations in protein content of the nuclear matrix, or other, more subtle alterations and/or modifications. The purpose of this investigation was to begin to determine how nuclear matrix protein composition is related to gene expression. We demonstrate that gene expression can change without apparent changes in the protein composition of the nuclear matrix in MCF10A breast epithelial cells.

Actins↗
PubMed1993

Clinicopathologic significance of p53 immunostaining in adenocarcinoma of the breast.

Methanol/acetone-fixed frozen sections of 87 breast carcinomas were studied with a panel of three anti-p53 monoclonal antibodies that had specificities for wild-type, mutant, or combined wild-type plus mutant epitopes by using the avidin-biotin method. Nuclear staining was present in 13 (15%) of 87 cases with the mutant-specific antibody. The combined-specificity antibody stained 28 (32%) of 87 cases, including all but one of the tumors that was positive with the mutant-specific antibody. None of the cases reacted with the wild-type-specific antibody. Immunostaining for mutant form p53 was strongly correlated with adverse clinicopathologic factors, including poor differentiation, absence of estrogen receptor protein, nodal metastases, and large tumor size. In groups that were stratified by axillary node status, disease-free survival (52-month mean follow-up) was worse among cases with positive staining for either antibody. This difference was statistically significant in node-positive patients with the combined-specificity antibody (disease free, 22% [p53+] vs recurred, 57% [p53+]). We concluded that (1) immunostaining for mutant forms of p53 characterizes a clinically aggressive subset of breast tumors and may have prognostic utility in some patient populations, and (2) antibody-dependent-staining patterns for p53 may reflect epitope specificities of various mutant forms.

Adenocarcinoma↗
PubMed1992

Analysis of retinoblastoma (RB) gene deletion in human prostatic carcinomas.

The retinoblastoma tumor suppressor gene (RB gene) has been reported to be deleted and/or modified in a number of human cancers, indicating that dysfunction of this tumor suppressor gene is perhaps critical in the development of many human tumors. In addition to deletion of one copy and/or mutational inactivation of the RB gene, this gene has also been reported to be altered by a small deletion in the promoter sequence in one case of small cell mixed adenocarcinoma of the prostate. A deletion of 105 nucleotides of the RB gene in exon 21, leading to an aberrant short-sized mRNA transcript, has also been reported in one cell line (DU 145) derived from brain metastasis of prostatic adenocarcinoma. We have analyzed tissues from 10 prostate specimens (3 hyperplastic and 7 neoplastic) and one prostate cancer cell line (DU 145) for the presence of short-sized mRNA transcript (exon 21 alterations) by polymerase chain reaction (PCR) using total RNA extracted from frozen tumors and the cell line. None of the prostate tissue showed any evidence of aberrant short-sized mRNA, although it was confirmed in the DU 145 cell line. Simultaneously, we have used DNA-PCR to investigate RB promoter deletion in 23 adenocarcinomas and one small cell carcinoma of the prostate. We also failed to demonstrate any indication of RB promoter deletion at the DNA level in adenocarcinomas. The single case of small cell carcinoma failed to show evidence of any aberration in RB promoter. We therefore conclude that neither RB promoter alterations nor the exon 21 deletion are associated with typical prostate adenocarcinoma.

Adenocarcinoma↗