PubMed · 13184727
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H D KAY. 1953. Recent light on mammary function.. https://pubmed.ncbi.nlm.nih.gov/13184727/
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LAF-4, which encodes a nuclear protein with transactivation potential, is fused to the MLL gene in acute lymphoblastic leukemia (ALL). We identified LAF-4 as a gene that is transcriptionally deregulated in breast tumors and thus may have a pathological role in mammary tumorigenesis. In line with the previous finding that LAF-4 expression is tissue specific, we did not detect any LAF-4 mRNA in normal mammary epithelial cell lines. However, 2 of 5 breast cancer cell lines were found to express LAF-4 at both the RNA and protein levels. In 2 of 9 primary tumor-normal pairs, the expression of LAF-4 was clearly elevated in the tumor tissue. Using RNA in situ hybridization, we demonstrated that LAF-4 is expressed in mammary tumor cells but not in normal acini. In a group of 64 primary human breast tumors, we found that LAF-4 was overexpressed in approximately 20% of the cases. Although epigenetic changes may be involved in altered expression of some genes, differences in LAF-4 expression were not associated with DNA methylation of the predicted promoter region. Our results suggest that LAF-4 may be a proto-oncogene that is transcriptionally activated in some cases of breast cancer.
We have used cultured human mammary epithelial cells (HMEC) and breast tumor-derived lines to gain information on defects that occur during breast cancer progression. HMEC immortalized by a variety of agents (the chemical carcinogen benzo(a)pyrene, oncogenes c-myc and ZNF217, and/or dominant negative p53 genetic suppressor element GSE22) displayed marked upregulation (10-15 fold) of the telomere-binding protein, TRF2. Upregulation of TRF2 protein was apparently due to differences in post-transcriptional regulation, as mRNA levels remained comparable in finite lifespan and immortal HMEC. TRF2 protein was not upregulated by the oncogenic agents alone in the absence of immortalization, nor by expression of exogenously introduced hTERT genes. We found TRF2 levels to be at least twofold higher than in control cells in 11/15 breast tumor cell lines, suggesting that elevated TRF2 levels are a frequent occurrence during the transformation of breast tumor cells in vivo. The dispersed distribution of TRF2 throughout the nuclei in some immortalized and tumor-derived cells indicated that not all the TRF2 was associated with telomeres in these cells. The process responsible for accumulation of TRF2 in immortalized HMEC and breast tumor-derived cell lines may promote tumorigenesis by contributing to the cells' ability to maintain an indefinite lifespan.
BACKGROUND: The evolution of procedures for reduction of breast volume and improvement of breast shape has been ongoing, based on the rich blood supply that has allowed a plethora of pedicle types. With particular consideration of the primary pattern of sensory innervation to the nipple-areola complex previously described, the authors have used the superolateral dermoparenchymal pedicle as a basis for surgery on a variety of presenting breast shapes. METHODS: This has been proven to be a versatile and effective technique for a wide array of breast morphologies with differing patterns of skin excision. The operative technique involves superior rotation of a superolaterally based dermoparenchymal pedicle, resulting in a "periwinkle" effect that provides desirable superior pole fullness and increased projection to the breast. RESULTS: More than 1500 breast procedures have been performed by the senior author (Strauch) during the past 15 years using the superolateral pedicle. Experience has demonstrated that the operation is safe, with total nipple-areola complex loss observed in only four cases. Long-term follow-up to 15 years has shown that the results are maintained well with time. CONCLUSIONS: The superolateral dermoparenchymal pedicle has fulfilled the goals of successful breast surgery. It is a safe and effective technique that has provided long-lasting results for patients. The design of the procedure can be adapted to a variety of skin excision patterns and breast morphologies.