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PTP LAR Expression Compared to Prognostic Indices in Metastatic and Non-Metastatic Breast Cancer (2000)

LeVea, Charles M. ; McGary, Carl T. ; Symons, Javelle R. ; [et al.]

Springer

Breast cancer research and treatment 64 (2000), S. 221-228

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ISSN: 1573-7217

Keywords: breast cancer ; EGF receptor ; erbB2 ; estrogen receptor ; LAR ; 13762NF tumor ; tyrosine phosphatase

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract Several prognostic indices in breast cancer, including c-erbB2, epithelial growth factor receptors (EGFR), estrogen and progesterone receptors are signal transduction molecules. Recently, expression of another signal transduction molecule, the protein tyrosine phosphatase LAR, has been suggested to be increased in breast cancer. The objective of the current investigation was to examine the relationship between LAR expression and prognostic parameters in breast cancer. LAR expression was associated with metastatic potential in the well-characterized 13762NF rat mammary adenocarcinoma clones. The metastatic MTLn3 and MTLn2 clones expressed sizable amounts of LAR. The essentially non-metastatic MTC clone had little LAR expression. C-erbB2 had highest expression in the highly metastatic MTLn3 clone, but c-erbB2 levels were sizeable in the weakly metastatic MTLn2 and non-metastatic MTC clone. EGFR expression had the strongest association with a clone's metastatic potential, being very high in MTLn3, weak in MTLn2, and undetectable in MTC. In human breast cancer specimens, LAR expression was strongly positive in 50% of metastatic cases but in only 21% of ‘non-metastatic’ cases. As with the 13762NF-derived clones, c-erbB2 expression was strongly positive independent of metastatic phenotype. However, 46% (6/13) of cases that were strongly positive for c-erbB2 were strongly positive for LAR. Only 17% (2/11) of negative or weakly c-erbB2 positive samples were strongly positive for LAR. All ER+ positive tumors (n = 15) were positive for LAR and 53% of these tumors were strongly positive for LAR. In ER− negative cases, only 1 of 11 was strongly positive for LAR. While the current data indicate a strong association between ER and LAR expression in breast cancer tissue (p = 0.003), additional studies are warranted to further explore the relationship between LAR and prognostic indices of breast cancer progression.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1006410509740

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The endocytic hyaluronan receptor in rat liver sinusoidal endothelial cells is Ca+2-independent and distinct from a Ca+2-dependent hyaluronan binding activity (1992)

Yannariello-Brown, Judith ; McGary, Carl T. ; Weigel, Paul H.

New York, N.Y. : Wiley-Blackwell

Journal of Cellular Biochemistry 48 (1992), S. 73-80

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ISSN: 0730-2312

Keywords: hyaluronic acid ; endocytosis ; recdptors ; calcium ions ; Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Isolated and cultured rat liver sinusoidal endothelial cells (LECs) retain the ability to specifically bind 125I-hyaluronan (HA) internalize it using a coated pit pathway [Biochem J, 257:875-884, 1989]. Here we have determined the effect of Ca+2 on the binding and endocytosis of HA by LECs. 125I-HA binding to intact LECs at 4°C occurred both in the absence (10 mM EGTA) or the presence of physiologic concentrations of Ca+2 (1.8 mM). However, the specific binding of 125I-HA to LECs increased linearly with increasing Ca+2 concentrations. After permeabilization with the nonionic detergent digitonin, the Ca+2-independent HA binding activity increased ∼743%, while the Ca+2-dependent binding activity was enhanced only ∼46%. Therefore, the Ca+2-dependent HA binding activity appears not to be intracellular, whereas the Ca+2-independent HA receptor is found both inside LECs and on the cell surface. When LECs were allowed to endocytose 125I-HA at 37°C in 10 mM EGT A or in 1.8 mM Ca+2, no differences were seen in the extent or rate of endocytosis. When LECs were allowed to endocytose 125I-HA in the presence of 10mM Ca125, the amount of cell-associated radiocctivity increased appoximately 20-50-fold. However, this additional cell-associated 125I-HA was not sensitive to hyperosmolarity and was removed by washing the cells in 10mM EGTA at 4°C. Therefore, the Ca+2-dependent cell-associated 125I-HA had accumulated on the cell surface and had not been internalized. From these studies we conclude the LECs have at least two trypes of specfic HA binding sites. One, the previously characterized HA receptor, is Ca+2-indepoendent, localized both extracellularly and intracellular, and medicates he efficient binding and subsequent endocytosis of HA using a coated pit pathway. The other newly recognized HA binding activity is Ca+2-dependent, localized wxtracellularly, and is not responsible for the endocytosis of HA in rat LECs.

Additional Material: 4 Ill.