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C L Arteaga

Publications and source records attributed to C L Arteaga.

At least 37 records · Page 2Linked to original sources
PubMed2000

Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in-situ and invasive carcinomas.

AIMS: Loss of transforming growth factor beta type II receptor (TGFbeta-RII) expression has been associated with resistance to TGFbeta-mediated inhibition of cell proliferation and tumour progression. We investigated whether the expression of TGFbeta-RII is related to the progression of human breast cancer and whether there is a correlation between TGFbeta-RII expression and phenotypic markers of biological aggressiveness. METHODS AND RESULTS: Immunohistochemical methods were used to detect TGFbeta-RII in archival breast samples including benign proliferative lesions, ductal carcinoma in situ (DCIS) and invasive mammary carcinomas (IMC). Neoplastic cells showed reduced expression of TGFbeta-RII in comparison to the normal breast tissue and benign lesions. There was a significant inverse correlation between loss of TGFbeta-RII expression and tumour grade within both DCIS (P = 0.004) and IMC (P = 0.001) groups. There was an inverse correlation between TGFbeta-RII expression and both mitotic count (P = 0.001) and clinical stage (P = 0.004). Oestrogen receptor (P = 0.07) and lymph node status (P = 0.10) were not significantly associated with TGFbeta-RII expression. CONCLUSIONS: These data indicate that decreased expression of TGFbeta-RII may contribute to breast cancer progression and is related to a more aggressive phenotype in both in-situ and invasive carcinomas.

Adult↗
PubMed2000

HER-2/neu (erbB-2) and the cell cycle.

Signaling by the HER-2 proto-oncogene product results in the activation of several biochemical pathways, which in turn modulate the expression and function of cell cycle regulators. These alterations of cell cycle regulatory molecules may be critical for the conception and maintenance of the transformed phenotype conferred by HER-2 gene amplification and overexpression. On the other hand, blockade of HER-2 function with a therapeutic intent will require the reversal of these effects on cell cycle regulatory molecules in order for these interventions to be effective. Data is presented to suggest that the G1 cyclin D1 and the cyclin-dependent kinase inhibitor p27KIP1 may be involved in subversion of the G1/S traverse by signaling pathways activated by HER-2 function.

Animals↗
PubMed1999

Transforming growth factor-beta and breast cancer risk in women with mammary epithelial hyperplasia.

BACKGROUND: Transforming growth factors-beta (TGF-betas) regulate mammary epithelial cell division. Loss of expression of TGF-beta receptor II (TGF-beta-RII) is related to cell proliferation and tumor progression. Breast epithelial hyperplastic lesions lacking atypia (EHLA) are associated with a mild elevation in breast cancer risk. We investigated the expression of TGF-beta-RII in EHLA and the risk of subsequent invasive breast cancer. METHODS: We conducted a nested case-control study of women with biopsy-confirmed EHLA who did not have a history of breast cancer or atypical hyperplasia of the breast. Case patients (n = 54) who subsequently developed invasive breast cancer were matched with control patients (n = 115) who did not. Formalin-fixed, paraffin-embedded sections of breast biopsy specimens of all 169 patients with EHLA were studied by immunohistochemical analysis with antibodies against TGF-beta-RII. All P values are two-sided. RESULTS: Women with breast EHLA and 25%-75% TGF-beta-RII-positive cells or less than 25% TGF-beta-RII-positive cells had odds ratios of invasive breast cancer of 1.98 (95% confidence interval [CI] = 0.95-4.1) or 3.41 (95% CI = 1.2-10.0), respectively (P for trend =.008). These risks are calculated with respect to women with EHLA that had greater than 75% TGF-beta-RII expression. Women with a heterogeneous pattern of TGF-beta-RII expression in their normal breast lobular units and either greater than 75%, 25%-75%, or less than 25% positive cells in their EHLA had odds ratios for breast cancer risk of 0.742 (95% CI = 0.3-1.8), 2.85 (95% CI = 1.1-7.1), or 3.55 (95% CI = 1.0-10.0), respectively (P for trend =.003). These risks are relative to women with a homogeneous pattern of expression in their normal lobular units and greater than 75% positive cells in their EHLA. CONCLUSION: This study indicates that loss of TGF-beta-RII expression in epithelial cells of EHLA is associated with increased risk of invasive breast cancer.

Adult↗
PubMed1999

Reversal of tamoxifen resistance of human breast carcinomas in vivo by neutralizing antibodies to transforming growth factor-beta.

BACKGROUND: Overexpression of transforming growth factor (TGF)-beta has been reported in human breast carcinomas resistant to antiestrogen tamoxifen, but the role of TGF-beta in this resistant phenotype is unclear. We investigated whether inhibition of TGF-beta2, which is overexpressed in LCC2 tamoxifen-resistant human breast cancer cells, could modify antiestrogen resistance. METHODS: TGF-beta2 expression was evaluated in LCC2 cells and tamoxifen-sensitive LCC1 cells by northern blot analysis. Secreted TGF-beta activity was quantified by use of an 125I-TGF-beta competitive radioreceptor assay. Sensitivity to tamoxifen was measured in a soft agarose colony-forming assay and in a xenograft model in nude and beige/nude mice. Natural killer (NK) cell cytotoxicity was measured by 51Cr release from LCC1 and LCC2 cell targets coincubated with human peripheral blood mononuclear cells. Decrease in TGF-beta2 expression in LCC2 cells was achieved by treatment with antisense oligodeoxynucleotides and confirmed by TGF-beta2 immunoblot analysis. RESULTS AND CONCLUSIONS: The proliferative response of LCC2 cells to tamoxifen in vitro was not altered by TGF-beta neutralizing antibodies. However, established LCC2 tumors in nude mice treated with tamoxifen plus TGF-beta antibodies failed to grow, whereas tumors treated with tamoxifen plus a control antibody continued to proliferate. This reversal of tamoxifen resistance by TGF-beta antibodies did not occur in beige/nude mice, which lack NK-cell function, suggesting that immune mechanisms may be involved in the antitumor effects of tamoxifen. Antisense TGF-beta2 oligodeoxynucleotides enhanced the NK sensitivity of LCC2 cells in the presence of tamoxifen. Finally, LCC1 tumors were markedly more sensitive to tamoxifen in NK-active than in NK-deficient mice. IMPLICATIONS: These data suggest that host NK function mediates, in part, the antitumor effect of tamoxifen and that TGF-beta2 may abrogate this mechanism, thus contributing to tamoxifen resistance.

Animals↗
PubMed1999

DNA polymerase beta expression differences in selected human tumors and cell lines.

A long-standing question in cancer biology has been the extent to which DNA repair may be altered during the process of carcinogenesis. We have shown recently that DNA polymerase beta (beta-pol) provides a rate-determining function during in vitro repair of abasic sites by one of the mammalian DNA base excision repair pathways. Therefore, altered expression of beta-pol during carcinogenesis could alter base excision repair and, consequently, be critical to the integrity of the mammalian genome. We examined the expression of beta-pol in several cell lines and human adenocarcinomas using a quantitative immunoblotting method. In cell lines from normal breast or colon, the level of beta-pol was approximately 1 ng/mg cell extract, whereas in all of the breast and colon adenocarcinoma cell lines tested, a higher level of beta-pol was observed. In tissue samples, colon adenocarcinomas had a higher level of beta-pol than adjacent normal mucosa. Breast adenocarcinomas exhibited a wide range of beta-pol expression: one tumor had a much higher level of beta-pol (286 ng/mg cell extract) than adjacent normal breast tissue, whereas another tumor had the same level of beta-pol as adjacent normal tissue. Differences in beta-pol expression level, from normal to elevated, were also observed with prostate adenocarcinomas. All kidney adenocarcinomas tested had a slightly lower beta-pol level than adjacent normal tissue. This study reveals that the base excision repair enzyme DNA polymerase beta is up-regulated in some types of adenocarcinomas and cell lines, but not in others.

Adenocarcinoma↗
PubMed1998

Blockade of tumor cell transforming growth factor-betas enhances cell cycle progression and sensitizes human breast carcinoma cells to cytotoxic chemotherapy.

We have examined the effect of neutralizing TGF-beta antibodies on cisplatin-mediated cytotoxicity against MDA-231 human breast tumor cell spheroids. These tridimensional in vitro systems have been shown to recapitulate the drug sensitivity pattern of tumor cells in vivo. MDA-231 tumor cell spheroids exhibit higher protein levels of the cyclin-dependent kinase (Cdk) inhibitors p21 and p27 and >10-fold lower Cdk2 activity compared to adherent cell monolayers, as well as pRb hypophosphorylation, a predominant G1 population, and a cisplatin 1-h IC50 of approximately 100 microM. Treatment of MDA-231 cells in monolayer with cisplatin for 1 h, subsequently grown as spheroids, increased steady-state TGF-beta1 mRNA levels, secretion of active TGF-beta, cellular Cdk2 activity, pRb phosphorylation, and p21 protein levels, while downregulating p27. Accumulation of cells in G2M and progression into S were noted 48 h after treatment with 100 microM cisplatin. We tested whether drug-induced upregulation of TGF-beta1 and p21, perhaps by preventing cell cycle progression, were protective mechanisms against drug-mediated toxicity by using neutralizing anti-TGF-beta antibodies. Anti-TGF-beta antibodies diminished the induction of p21, enhanced the activation of Cdk2, and facilitated progression into S and G2M following cisplatin treatment. This resulted in a >twofold enhancement of drug-induced DNA fragmentation and a shift in the cisplatin 1-h IC50 from 100 to <10 microM. These data suggest that tumor cell TGF-beta1 may protect from DNA damage and that postchemotherapy administration of TGF-beta inhibitors may facilitate progression beyond G1/S, potentially increasing the efficacy of cytotoxic chemotherapy.

Antineoplastic Agents↗
PubMed1998

Down-regulation of type I protein kinase A by transfection of human breast cancer cells with an epidermal growth factor receptor antisense expression vector.

MDA-468 human breast cancer cells overexpress the EGFR and exhibit a functional TGFalpha-EGFR autocrine pathway. Loss of EGFR expression following stable transfection with an antisense EGFR cDNA containing plasmid down-regulates type I cAMP-dependent protein kinase (PKAI) expression with acquisition of cell growth resistance to the PKAI inhibitor 8-Cl-cAMP. These results suggest that PKAI expression and function are controlled by a TGFalpha-EGFR autocrine pathway in human breast cancer cells overexpressing the EGFR.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

A kinase-defective transforming growth factor-beta receptor type II is a dominant-negative regulator for human breast carcinoma MCF-7 cells.

The role of transforming growth factor (TGF)-beta type II receptor (T beta RII) in TGF-beta resistance and tumor progression is now well recognized. To test the effects of T beta RII loss in determining malignancy, we transfected a T beta RII-expressing, TGF-beta-sensitive, MCF-7 cell strain (ME24) with a tetracycline-repressible truncated T beta RII (kdT beta RII) construct lacking the cytoplasmic domain of the receptor. Transfection of kdT beta RII into parental ME24 cells (designated ME24t6 after transfection) resulted in high expression levels of kdT beta RII mRNA and cell surface protein which were reversible by tetracycline treatment. ME24t6 cells did not respond to exogenous TGF-beta 1 as measured by inhibition of proliferation or fibronectin (FN) induction, indicating that the truncated T beta RII acted as a dominant-negative inhibitor of both the growth inhibitory and extracellular matrix (ECM) stimulatory TGF-beta effects. Furthermore, inhibition of kdT beta RII expression by tetracycline treatment led to TGF-beta 1-mediated cell growth arrest in the G1 phase of cell cycle and to the accumulation of the hypophosphorylated form of retinoblastoma (Rb) protein. However, compared to parental ME24 cells, transfectants failed to show increased tumorigenicity, indicating that loss of T beta RII itself is not sufficient to account for differences in the malignant properties of T beta RII-expressing and non-expressing MCF-7 cell strains.

Adenocarcinoma↗
PubMed1998

Protein kinase C epsilon translocation and phosphorylation by cis-diamminedichloroplatinum(II) (CDDP): potential role in CDDP-mediated cytotoxicity.

Phorbol ester-like protein kinase C (PKC) activators, such as 12-O-tetradecanoylphorbol-13-acetate, and perturbation of some growth factor receptors have been reported to alter the cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP). To study the mechanism of this alteration, we have examined the effect of CDDP per se on PKC isozymes. The SKBR-3 human breast carcinoma cell line exhibits at least six different PKC isozymes (PKC alpha, betaI, betaII, delta, epsilon, and zeta). After exposure to 10-100 microM CDDP for 3 h, only PKC epsilon translocated from the plasma membrane to the nuclear membrane and to the cytosolic fraction. This translocation was observed in a time- and dose-dependent manner by Western blot and confocal microscopy. CDDP also decreased the mobility of PKC epsilon in the nuclear membrane fraction, an effect that was blocked by protein phosphatase 2A, suggesting drug-mediated isozyme phosphorylation. This translocation and phosphorylation were also induced by the cisplatin analogue carboplatin but not with the anticancer agents Adriamycin and Taxol. Antisense oligodeoxynucleotides against PKC epsilon down-regulated isozyme content, blocked drug-induced translocation, and reduced cisplatin-mediated cytotoxicity 3-fold compared to that of sense-treated cells. Antisense PKC epsilon also decreased SKBR-3 cell sensitivity to carboplatin but not to Adriamycin and Taxol. These data support a role for PKC epsilon translocation and phosphorylation on CDDP-mediated toxicity.

Antineoplastic Agents↗
PubMed1997

Unliganded epidermal growth factor receptor dimerization induced by direct interaction of quinazolines with the ATP binding site.

Receptor dimerization is critical for signaling by the epidermal growth factor receptor (EGFR) tyrosine kinase. This occurs after binding of the receptor's extracellular domain by ligand or bivalent antibodies. The role of other receptor domains in dimerization is less clear, and there are no examples of dimers induced by direct perturbation of the EGFR kinase domain. Submicromolar concentrations of AG-1478 and AG-1517, quinazolines specific for inhibition of the EGFR kinase, induced reversible receptor dimerization in vitro and in intact A431 cells. Consistent with the inhibitory effect of quinazolines on receptor kinase activity, the dimers formed lacked a detectable Tyr(P) signal. Quinazoline-induced EGFR dimerization was abrogated in vitro by ATP and the ATP analog adenyl-5'-yl imidodiphosphate. Receptors with a single-point mutation in the ATP binding site as well as wild-type EGFR with a covalent modification of the ATP site failed to dimerize in response to AG-1478 and AG-1517. These data suggest that EGFR dimerization can be induced by the interaction of quinazolines at the ATP site in the absence of receptor ligand binding. In SKBR-3 cells, the quinazolines induced the formation of inactive EGFR/ErbB-2 heterodimers, potentially sequestering ErbB-2 from interacting with other coreceptors of the ErbB family. Structural studies of the quinazoline interaction with the EGFR tyrosine kinase domain should allow for an analysis of receptor-specific chemical features required for binding to the ATP site and disruption of signaling, a strategy that can be perhaps applied to other tumor cell receptor systems.

Adenosine↗
PubMed1997

Blockade of transforming growth factor-beta signaling does not abrogate antiestrogen-induced growth inhibition of human breast carcinoma cells.

We have studied the role of autocrine transforming growth factor-beta (TGF-beta) signaling on antiestrogen-mediated growth inhibition of hormone-dependent T47D and MCF-7 human breast carcinoma cells. Tamoxifen treatment increased the secretion of TGF-beta activity into serum-free cell medium and the cellular content of affinity cross-linked type I and III TGF-beta receptors in both cell lines. Anti-pan-TGF-beta antibodies did not block anti-estrogen-induced recruitment in G1 and inhibition of anchorage-dependent and -independent growth of both cell lines. Early passage MCF-7 cells, which exhibit detectable type II TGF-beta receptors at the cell surface and exquisite sensitivity to exogenous TGF-beta1, were transfected with a tetracycline-controllable dominant-negative TGF-betaRII (DeltaRII) construct. Although the TGF-beta1 response was blocked by removal of tetracycline in MCF-7/DeltaRII cells, tamoxifen-mediated suppression of Rb phosphorylation, recruitment in G1, and inhibition of cell proliferation were identical in the presence and absence of tetracycline. TGF-beta1 treatment up-regulated the Cdk inhibitor p21 and induced its association with Cdk2 in MCF-7 cells; these responses were blocked by the DeltaRII transgene product. In MCF-7 cells with a functional TGF-beta signaling pathway, tamoxifen did not up-regulate p21 nor did it induce association of p21 with Cdk2, suggesting alternative mechanisms for antiestrogen-mediated cytostasis. Finally, transfection of late-passage, TGF-beta1 unresponsive MCF-7 cells with high levels of TGF-betaRII restored TGF-beta1-induced growth inhibition but did not enhance tamoxifen response in culture. Taken together these data strongly argue against any role for TGF-beta signaling on tamoxifen-mediated growth inhibition of hormone-dependent breast cancer cells.

Breast Neoplasms↗
PubMed1997

Processing of the transforming growth factor beta type I and II receptors. Biosynthesis and ligand-induced regulation.

Three cell surface transforming growth factor beta (TGFbeta) receptor (R) proteins regulate the effects of TGFbeta isoforms on growth and differentiation. TGFbeta-IR and -IIR are transmembrane serine/threonine kinases directly mediating the signaling across the plasma membrane. Both TGFbeta and its receptors are ubiquitously expressed, hence the fine regulation of the multiplicity of responses most likely involves several levels of control including the regulation of expression, complex formation, and down-regulation of the receptor proteins. In mink lung epithelial cells, TGFbeta-IIR was first synthesized as a approximately 60-kDa endoglycosidase H-sensitive precursor protein, which was converted to a mature approximately 70-kDa protein. The half-life of metabolically labeled mature TGFbeta-IIR was estimated to be 60 min and was further reduced to approximately 45 min in the presence of exogenous TGFbeta1. Minimal internalization of 125I-TGFbeta1 at 37 degrees C was detected suggesting that the rapid turnover was not due to endocytosis and degradation of the ligand-receptor complexes. TGFbeta-IR was synthesized as a approximately 53-kDa precursor protein, which was processed to a mature approximately 55-kDa receptor protein. The half-life of TGFbeta-IR was >12 h. A fraction of tunicamycin-treated type I and II receptors that reach the cell surface was able to associate in the presence of ligand suggesting that heteromeric complexes can form in a post-endoplasmic reticulum compartment before full glycosylation is achieved. These results show differential processing and turnover of TGFbeta-IR and TGFbeta-IIR providing a potential additional mechanism for modulation of cellular responses to TGFbetas.

Activin Receptors, Type I↗
PubMed1997

Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA.

BACKGROUND: Epidermal growth factor receptor (EGF-R) perturbation by receptor ligand(s), e.g., epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), or receptor-specific antibodies accentuates cisplatin-induced toxicity in tumor cells. This sensitization occurs only in tumor cells with high expression of EGF-R but not in those with low expression of EGF-R. PURPOSE: Therefore, we have studied the role of EGF-R expression on cisplatin-mediated cytotoxicity. METHODS: MDA-468 human breast cancer cells were stably transfected with a p-chloramphenicol acetyl transferase (pact[p]-CAT) vector containing a 4.1-kilobase full-length antisense EGF-R complementary DNA. EGF-R content was assessed by 125I-EGF binding and EGF-R immunoblot assays. Cisplatin sensitivity was evaluated by (a) colony-forming assay in vitro, (b) xenograft growth in nude mice, (c) cell cycle distribution of propidium iodide-labeled DNA, (d) DNA fragmentation in agarose gels, and (e) terminal deoxynucleotidyl transferase (Tdt) fluorescence in situ. Cisplatin uptake was measured by atomic absorption spectroscopy, and the levels of drug-DNA intrastrand adducts were determined by a dissociation-enhanced fluoroimmunoassay that utilizes an antibody against cisplatin-modified DNA. RESULTS: Selected clones (MDA-468/AS-EGFR) exhibited more than 90% loss of both 125I-EGF binding and receptor content determined by western blot analysis, whereas clones transfected with the vector alone (MDA-468/p-CAT) had EGF-R levels similar to those of the parent cells. By use of a colony-forming assay, the 1-hour IC50 (i.e., the concentration of drug required for 1 hour to achieve 50% cell kill) for cisplatin was 2 microM or less for parental and vector-transfected clones (n = 4), whereas it was 25 microM or more for all MDA-468/AS-EGFR clones (n = 3). MDA-468/p-CAT clones exhibited internucleosomal DNA fragmentation, enhanced Tdt-end labeling in situ, and G2 arrest 48 hours after a 1-hour incubation with 3-30 microM cisplatin. Under these conditions, apoptosis and G2 arrest were undetectable in all MDA-468/AS-EGFR clones. An MDA-468 subline selected after long-term treatment with a TGF-alpha-Pseudomonas exotoxin A fusion protein 40 lacked EGF binding and also exhibited cisplatin resistance (1-hour IC50: > 30 microM) compared with parental cells. This EGF-R-dependent difference in cisplatin response was confirmed in a nude mouse xenograft model by use of high- and low-EGF-R-expressing cell clones. Total intracellular drug accumulation after a 1-hour cisplatin exposure, as measured by atomic absorption spectroscopy, was identical in both groups of cells. Intrastrand drug-DNA adducts, however, were statistically higher in high EGF-R expressors than in low-EGF-R-expressing clones. CONCLUSIONS: These data indicate that a critical level of EGF-R signaling, which is amplified in some common human cancers, is necessary for cisplatin-mediated apoptosis in tumor cells and suggest an inhibitory effect of this pathway on the repair of cisplatin-damaged DNA.

Animals↗
PubMed1997

Predominant cytosolic localization of type II transforming growth factor beta receptors in human breast carcinoma cells.

It is proposed that loss of a growth-inhibitory response to transforming growth factor beta (TGFbeta) contributes to breast cancer progression. Because cellular TGFbeta responsiveness often correlates with TGFbeta type II receptor (TGFbeta-IIR) expression, we have examined the cellular distribution of TGFbeta-IIRs in tumor and nontumor mammary epithelial cells. By immunoblot analysis, TGFbeta-IIR was detected both in membrane and cytosolic fractions of MDA-231 tumor cells as well as in normal human breast epithelial cells. The cytosolic protein appeared to be more abundant and was detected as a clear perinuclear staining by immunocytochemistry. The glycosylation patterns of the cytosolic and membrane form were different, indicating distinct receptor pools. The cytosolic TGFbeta-IIR did not bind 125I-labeled TGFbeta1 but had a detectable in vitro and in vivo kinase activity. MCF-7 breast cancer cells express the TGFbeta-IIR mRNA but show undetectable cell surface TGFbeta-IIR protein by affinity cross-linking. However, low levels of TGFbeta-IIR were observed in MCF-7 cytosol. Sequencing of the coding region of TGFbeta-IIR from MCF-7 cells indicated a point mutation (A439V) in a nonconserved region of the kinase domain. When MCF-7 cells were treated with sublethal doses of Adriamycin that induce cell differentiation, the membrane localization of TGFbeta-IIR and TGFbeta response were restored. Our results indicate the presence of a prominent, kinase-active TGFbeta-IIR in the cytosol of several mammary cell lines. This cytosolic pool of receptors is the only detectable one in MCF-7 cells. Loss of wild-type membrane receptors due to defects in trafficking presents a potential new mechanism for escape from negative growth control.

Biological Transport↗
PubMed1996

Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice.

The c-fos proto-oncogene has been implicated as a regulator of estrogen-mediated cell proliferation. We have tested the tissue specificity and antitumor efficacy of a mouse mammary tumor virus-regulated antisense c-fos retroviral vector. Systemically administered vector could be detected in several tissues but was only expressed in breast epithelium, thus supporting targeting to mouse mammary tumor virus-regulated tissues. Ex vivo transduction of 30-70% of MCF-7 human breast cancer cells produced expression of antifos RNA, decreased expression of the c-fos target mRNA, induction of differentiation, and inhibition of s.c. tumor growth and invasiveness. In vivo transduction of established i.p. MCF-7 tumors with a single injection of XM6:antifos inhibited tumor growth in athymic mice with a corresponding inhibition of c-fos, transforming growth factor beta1 and transforming growth factor alpha expression. Four daily injections with the antifos RNA induced a much larger MCF-7 i.p. tumor inhibition, with a marked prolongation of survival in the absence of any host tissue toxicity. These results indicate that inhibition of key nuclear genes such as c-fos may lead to disruption of paracrine factors and an antitumor effect, providing a strategy for cancer gene therapy.

Animals↗
PubMed1996

The multifunctional role of transforming growth factor (TGF)-beta s on mammary epithelial cell biology.

The transforming growth factor-beta s are potent growth inhibitors of normal and transformed breast epithelial cells in culture. In vivo, these peptides modulate the development of the mouse mammary gland. Tissue-specific overexpression of mature TGF-beta 1 in transgenic mice results in mammary gland atrophy and prevention of carcinogen-induced breast tumorigenesis. However, the inhibitory effect of endogenous or exogenous TGF-beta s on established tumor cells is less clear. Several published circumstantial and more direct data argue that, in some cases, the tumor cell TGF-beta s may contribute to the maintenance and/or progression of tumor cells in an intact host by modulating their interaction with host factors. This differential role of the TGF-beta s on mammary cells as determined by their normal or transformed phenotype as well as the biological and clinical implications of these data are discussed.

Animals↗