PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9371489

Progressive decrease in nuclear retinoic acid receptor beta messenger RNA level during breast carcinogenesis.

X C Xu·N Sneige·X Liu·R Nandagiri·J J Lee·F Lukmanji·G Hortobagyi·S M Lippman·K Dhingra·R Lotan
View original source ↗Export metadata ↓

Abstract

Some of the nuclear retinoic acid receptors (RARs) alpha, beta, and gamma and retinoid X receptors (RXRs) alpha, beta, and gamma are thought to mediate the effects of retinoids on cell growth, differentiation, and apoptosis and thereby prevent breast carcinogenesis. We analyzed the expression of mRNAs for the three RARs and RXR-alpha in histological sections of specimens from 70 breast cancer patients, which included adjacent normal tissue, ductal carcinoma in situ, and invasive cancer, using in situ hybridization. RARs alpha, beta, and gamma and RXR-alpha were expressed in 98.1, 98.0, 93.0, and 100% of the adjacent normal tissues. Significant decreases in the number of cases expressing RAR-beta were observed among ductal carcinoma in situ (83.1%) and invasive carcinomas (51.6%), especially among the poorly differentiated cases (77.4 and 35.7 %, respectively). No relationship was found between the expression of estrogen receptor and RAR-beta. These results implicate decreases in RAR-beta expression in breast cancer development and suggest that they are independent of estrogen receptor status.

Explore related subjects

BreastBreast NeoplasmsCarcinoma in SituCarcinoma, Ductal, BreastFemaleHumansNeoplasm ProteinsRNA, MessengerReceptors, Retinoic AcidJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

X C Xu, N Sneige, X Liu, R Nandagiri, J J Lee, F Lukmanji, G Hortobagyi, S M Lippman, K Dhingra, R Lotan. 1997-11-15. Progressive decrease in nuclear retinoic acid receptor beta messenger RNA level during breast carcinogenesis.. https://pubmed.ncbi.nlm.nih.gov/9371489/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1998

The estrogen receptor variant lacking exon 5 has dominant negative activity in the human breast epithelial cell line HMT-3522S1.

The estrogen receptor variant lacking exon 5 (ERdeltaE5) encodes a truncated protein that lacks the hormone-binding domain and has been suggested to be responsible for the estrogen-independent growth of human breast tumors and resistance to antiestrogen therapy. The biological function of the ERdeltaE5 in human breast epithelial cells has been studied by transient transfection of HMT-3522S1 cells with wild-type (wt) estrogen receptor (ER) and ERdeltaE5. A 10-fold higher expression of ERdeltaE5 mRNA compared to that of wt ER mRNA was found. However, the expression of ERdeltaE5 protein was significantly lower than the expression of wt ER protein. The ERdeltaE5 was unable to activate the transcription of an estrogen-responsive reporter gene in the absence as well as in the presence of estrogen. The ERdeltaE5 disclosed a dominant negative activity when expressed together with wt ER. These data indicate that the biological significance of ERdeltaE5 in human breast cancer is dubious.

Breast↗
PubMed1998

Loss of p16INK4 expression by methylation is associated with lifespan extension of human mammary epithelial cells.

Inactivation of p16INK4 tumor suppressor gene function is frequently observed in breast cancer. We examined p16INK4 expression in human mammary epithelial cell (HMEC) cultures established from four normal donors. Normal HMECs divide a limited number of times before proliferation ceases in a state referred to as selection (or M0). The cell subpopulation that emerges spontaneously from selection undergoes a further limited period of proliferation before senescence. By immunofluorescence and Western blot analysis of four independent cultures, we have shown loss of p16INK4 expression in postselection HMECs. In contrast, p16INK4 was present in both early and late passage fibroblasts from the same individuals. Bisulfite genomic sequencing revealed extensive methylation of the p16INK4 CpG island in post- but not preselection cells. Thus, the extended period of growth observed in postselection HMECs is associated with hypermethylation of the p16INK4 CpG island and loss of p16INK4 expression. Although postselection HMECs are widely considered to be normal, these data indicate that they have sustained an epigenetic alteration.

Breast↗