HER2 Support Group Forums - View Single Post - testosterone

Rich66 · 11-14-2009, 10:20 PM

Not sure how to interpret the info but testosterone/androgens seem to be studies in BC:

Steroids. 2009 Oct 24. [Epub ahead of print]
Conjugated and non-conjugated androgens differentially modulate specific early gene transcription in breast cancer in a cell-specific manner.

Notas G, Pelekanou V, Castanas E, Kampa M.
Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion GR-71003, Greece.
The role of androgen in breast cancer development is not fully understood, although androgen receptors (ARs) have been identified in breast cancer clinical samples and cell lines. However the whole spectrum of androgen actions cannot be accounted to the classic AR activation and the possible existence of a cell surface-AR has been suggested. Indeed, androgen, like all steroids, has been reported to trigger membrane-initiated signaling activity and exert specific actions, including ion channels and kinase signaling pathway activation, ultimately affecting gene expression. However, the molecular nature of membrane androgen sites represents another major persisting question. In the present study, we investigated early transcriptional effects of testosterone and the impermeable testosterone-BSA conjugate, in two breast cancer cell lines (T47D and MDA-MB-231), in an attempt to decipher specific genes modified in each case, providing evidences about specific membrane-initiating actions. Our data indicate that the two agents affect the expression of several genes. A group of genes were commonly affected while others were uniquely modified by each agent, including interaction with growth factors and K(+)-channels. In MDA-MB-231 cells, that are AR negative, the majority of genes affected by testosterone were also affected by testosterone-BSA indicating a membrane-initiated action. Subsequent analysis revealed that the two agents trigger different molecular pathways and cellular/molecular functions, suggestive of a molecular or functional heterogeneity of membrane and intracellular AR. In addition, the reported phenotypic interactions of membrane-acting androgen with growth factor were verified at the transcriptomic level, as well as their ion channel-modifying effects. Finally an interesting interplay between membrane-acting androgen with inflammation-related molecules, with potential clinical implications was revealed.

PMID: 19857505 [PubMed - as supplied by publisher]

Exp Cell Res. 2005 Jul 1;307(1):41-51. Epub 2005 Apr 7.
Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis.

Kampa M, Nifli AP, Charalampopoulos I, Alexaki VI, Theodoropoulos PA, Stathopoulos EN, Gravanis A, Castanas E.
Department of Experimental Endocrinology, University of Crete, School of Medicine, P.O. Box 2208, Heraklion, GR-71003, Greece.
Classical steroid mode of action involves binding to intracellular receptors, the later acting as ligand-activated nuclear transcription factors. Recently, membrane sites for different steroids have been also identified, mediating rapid, non-genomic, steroid actions. Membrane sites for estrogen and androgen have been found in a number of different cell types, bearing or not classical intracellular receptors. In the present study, with the use of radioligand binding, flow cytometry and confocal laser microscopy, we report that T47D human breast cancer cells express specific and saturable membrane receptors for both estrogen (K(D) 4.06 +/- 3.31 nM) and androgen (K(D) 7.64 +/- 3.15 nM). Upon activation with BSA-conjugated, non-permeable ligands (E(2)-BSA and testosterone-BSA), membrane estrogen receptors protect cells from serum-deprivation-induced apoptosis, while androgen receptors induce apoptosis in serum-supplemented T47D cells. In addition, co-incubation of cells with a fixed concentration of one steroid and varying concentrations of the other reversed the abovementioned effect (apoptosis for androgen, and anti-apoptosis for E(2)), suggesting that the fate of the cell depends on the relative concentration of either steroid in the culture medium. We also report the identification of membrane receptors for E(2) and androgen in biopsy slides from breast cancer patients. Both sites are expressed, with the staining for membrane E(2) being strongly present in ER-negative, less differentiated, more aggressive tumors. These findings suggest that aromatase inhibitors may exert their beneficial effects on breast cancer by also propagating the metabolism of local steroids towards androgen, inducing thus cell apoptosis through membrane androgen receptor activation.

PMID: 15922725 [PubMed - indexed for MEDLINE]

11-14-2009, 10:20 PM	#3
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: testosterone - CAN IT HELP? Not sure how to interpret the info but testosterone/androgens seem to be studies in BC: Steroids. 2009 Oct 24. [Epub ahead of print] Conjugated and non-conjugated androgens differentially modulate specific early gene transcription in breast cancer in a cell-specific manner. Notas G, Pelekanou V, Castanas E, Kampa M. Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion GR-71003, Greece. The role of androgen in breast cancer development is not fully understood, although androgen receptors (ARs) have been identified in breast cancer clinical samples and cell lines. However the whole spectrum of androgen actions cannot be accounted to the classic AR activation and the possible existence of a cell surface-AR has been suggested. Indeed, androgen, like all steroids, has been reported to trigger membrane-initiated signaling activity and exert specific actions, including ion channels and kinase signaling pathway activation, ultimately affecting gene expression. However, the molecular nature of membrane androgen sites represents another major persisting question. In the present study, we investigated early transcriptional effects of testosterone and the impermeable testosterone-BSA conjugate, in two breast cancer cell lines (T47D and MDA-MB-231), in an attempt to decipher specific genes modified in each case, providing evidences about specific membrane-initiating actions. Our data indicate that the two agents affect the expression of several genes. A group of genes were commonly affected while others were uniquely modified by each agent, including interaction with growth factors and K(+)-channels. In MDA-MB-231 cells, that are AR negative, the majority of genes affected by testosterone were also affected by testosterone-BSA indicating a membrane-initiated action. Subsequent analysis revealed that the two agents trigger different molecular pathways and cellular/molecular functions, suggestive of a molecular or functional heterogeneity of membrane and intracellular AR. In addition, the reported phenotypic interactions of membrane-acting androgen with growth factor were verified at the transcriptomic level, as well as their ion channel-modifying effects. Finally an interesting interplay between membrane-acting androgen with inflammation-related molecules, with potential clinical implications was revealed. PMID: 19857505 [PubMed - as supplied by publisher] Exp Cell Res. 2005 Jul 1;307(1):41-51. Epub 2005 Apr 7. Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis. Kampa M, Nifli AP, Charalampopoulos I, Alexaki VI, Theodoropoulos PA, Stathopoulos EN, Gravanis A, Castanas E. Department of Experimental Endocrinology, University of Crete, School of Medicine, P.O. Box 2208, Heraklion, GR-71003, Greece. Classical steroid mode of action involves binding to intracellular receptors, the later acting as ligand-activated nuclear transcription factors. Recently, membrane sites for different steroids have been also identified, mediating rapid, non-genomic, steroid actions. Membrane sites for estrogen and androgen have been found in a number of different cell types, bearing or not classical intracellular receptors. In the present study, with the use of radioligand binding, flow cytometry and confocal laser microscopy, we report that T47D human breast cancer cells express specific and saturable membrane receptors for both estrogen (K(D) 4.06 +/- 3.31 nM) and androgen (K(D) 7.64 +/- 3.15 nM). Upon activation with BSA-conjugated, non-permeable ligands (E(2)-BSA and testosterone-BSA), membrane estrogen receptors protect cells from serum-deprivation-induced apoptosis, while androgen receptors induce apoptosis in serum-supplemented T47D cells. In addition, co-incubation of cells with a fixed concentration of one steroid and varying concentrations of the other reversed the abovementioned effect (apoptosis for androgen, and anti-apoptosis for E(2)), suggesting that the fate of the cell depends on the relative concentration of either steroid in the culture medium. We also report the identification of membrane receptors for E(2) and androgen in biopsy slides from breast cancer patients. Both sites are expressed, with the staining for membrane E(2) being strongly present in ER-negative, less differentiated, more aggressive tumors. These findings suggest that aromatase inhibitors may exert their beneficial effects on breast cancer by also propagating the metabolism of local steroids towards androgen, inducing thus cell apoptosis through membrane androgen receptor activation. PMID: 15922725 [PubMed - indexed for MEDLINE] __________________ Mom's treatment history (link)