The African Organization for Research and Training in Cancer: historical perspective.

The African Organization for Research and Training in Cancer (aortic) is a bilingual (English and French) nonprofit organization dedicated to the promotion of cancer control and palliation in Africa. Its mission in respect to cancer control in Africa includes support of research and training;provision of relevant and accurate information on the prevention, early diagnosis, treatment, and palliation of cancer;promotion of public awareness about cancer and reduction of the stigma associated with it.In seeking to achieve its goal of cancer control in Africa, aortic strives to unite the continent and to make a positive impact throughout the region by collaboration with health ministries and global cancer organizations. The organization's key objectives are to further research relating to cancers prevalent in Africa, to support training programs in oncology for health care workers, to deal with the challenges of creating cancer control and prevention programs, and to raise public awareness of cancer in Africa. It also plans to organize symposia, workshops, meetings, and conferences that support its mission.Founded in September 1982, aortic was active only between 1983 (when its inaugural conference was held in the City of Lome, Togo, West Africa) and the late 1980s. The organization subsequently became inactive and moribund. In 2000, a group of expatriate African physicians and scientists joined in an effort with their non-African friends and colleagues to reactivate the dormant organization. Since its reactivation, aortic has succeeded in putting cancer on the public health agenda in many African countries by highlighting Africa's urgent need for cancer control and by holding meetings every two years in various African cities. National and international cancer control organizations worldwide have recognized the challenges facing Africa and have joined in aortic's mission.

Effect of acid on duodenal blood flow and mucus secretion measured by reflectance spectrophotometry: a prospective, randomized-controlled study.

BACKGROUND: In animals, hydrochloric acid increases blood flow and mucus secretion in the duodenal mucosa. A significant correlation between index of haemoglobin oxygen saturation and mucosal blood flow, and between change in index of haemoglobin concentration and mucus thickness, respectively, has been demonstrated by reflectance spectrophotometry. AIM: To examine the effect of topical hydrochloric acid upon mucosal blood flow and mucus secretion in the human duodenum. METHODS: This prospective study of 120 patients undergoing routine upper endoscopy, examined the effect of topical 0.1 n hydrochloric acid or 0.9% saline on the duodenal bulb in a randomized, double-blind fashion. Duodenal mucosal index of haemoglobin oxygen saturation and index of haemoglobin concentration were measured by endoscopic reflectance spectrophotometry before and after hydrochloric acid or saline. RESULTS: Baseline index of haemoglobin oxygen saturation, calculated blood flow and index of haemoglobin concentration measurements were comparable between hydrochloric acid (n = 60) and saline (n = 60) treated groups. A history of current use of non-steroidal anti-inflammatory drug was associated with a significantly lower baseline index of haemoglobin oxygen saturation and calculated blood flow. Hydrochloric acid resulted in a significant increase in index of haemoglobin oxygen saturation and calculated blood flow, but a decrease in index of haemoglobin concentration, reflecting an increase in mucus thickness compared with saline. CONCLUSIONS: Our observations in humans confirm data in animal studies that topical exposure to hydrochloric acid induces an increase in duodenal mucosal blood flow and mucus secretion. Post hoc analysis of the data also revealed that attenuation of basal duodenal mucosal blood flow is associated with a history of current non-steroidal anti-inflammatory drug use. Endoscopic reflectance spectrophotometry appears to be adequate to assess factors that influence duodenal defence mechanisms of blood flow and mucus secretion in humans.

High prevalence of MMTV-like env gene sequences in gestational breast cancer.

Gestational breast cancer (BC) is generally associated with rapid growth and increased mortality. Because the presence of MMTV-like sequences in BC has been associated with laminin receptor expression, a marker of poor prognosis, gestational BCs were analyzed for MMTV env gene-like sequences to explore whether MMTV-like sequences were also associated with its adverse outcome. Whereas 30-38% of sporadic BC have the sequences, in gestational BC the prevalence is 62%. We suggest that hormonal response elements present in the MMTV-like LTR may play a role in promoting cell growth, as they do in the mouse system.

Putative protein markers in the sera of men with prostatic neoplasms.

OBJECTIVE: To describe the preliminary identification of serum proteins that may be diagnostic markers in prostate cancer. PATIENTS AND METHODS: The study included 11 men referred for treatment of localized prostate cancer, 12 with benign prostatic hyperplasia (BPH) and 12 disease-free controls. For serum protein analysis, the protein-chip array surface-enhanced laser desorption/ionization (SELDI) technique was used (Ciphergen Biosystems, Fremont, CA). SELDI combines protein-chip technology with time-of-flight mass spectrometry, and offers the advantages of speed, simplicity and sensitivity. RESULTS: Three protein peaks were identified in the serum of men with prostate cancer and BPH, but not in controls, with relative molecular masses of 15.2, 15.9 and 17.5 kDa. These three proteins were significantly associated with BPH and prostate cancer when compared with controls (P = 0.001, 0.004, and 0.011, respectively, Kruskal-Wallis test). Interestingly, the 17.5 kDa protein was more abundant in five men with stage T1 prostate cancer than in eight with stage T2 (P = 0.016, two tailed Mann-Whitney U-test corrected for ties). CONCLUSIONS: These proteins, particularly the 15.9 kDa one, may be used for the diagnosis or monitoring of prostate cancer and differentiation from BPH, and have the potential for antibody-based chip SELDI-TOF technology. Identified proteins may be targets for immunotherapy.

Stable lower PAR expression decreased DU145 prostate cancer cell growth in SCID mice.

BACKGROUND: PAR is a novel gene ubiquitously expressed in normal and malignant tissues with a trend towards higher expression in tumor cells. PAR biological function is unknown. Here we report the effect of lowering PAR expression on in vitro and in vivo proliferation of DU145 cells. METHODS: Decreased PAR expression was achieved by stable transfection of DU145 cells with antisense PAR cDNA cloned in pCMV-Script expression vector. The proliferative potential of DU145 transfectants was studied by cell counts, colony formation in soft agar, flow cytometry, and growth in severe combined immunodeficient (SCID) mice. RESULTS: DU145 transfectants exhibited a decreased cell proliferation in tissue culture and a low efficiency of colony formation in soft agar. Flow cytometry revealed an arrest of these cells in G2-M phase of mitotic cycle. A dramatic decrease of tumor growth was observed when DU145 transfectant cells were inoculated in SCID mice, compared with controls. Histological examination of these tumors showed a marked decrease in cell density and in number of mitoses while control tumors showed a high cell density and numerous mitoses. CONCLUSIONS: The data presented here provide the first evidence for PAR gene cellular function and its possible implication in malignant transformation.

High anticancer efficacy of L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13) in vivo.

The anticancer efficacy of the new anticancer tripeptide, L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13), was investigated in mice. MF13 showed a therapeutic effect in liquid tumors and induced complete remission even in late stage malignancies. MF13 also inhibited human colon cancer growth in nude mice by more than 85% (volume, p<0.001). It acted in a dose-dependent manner and induced a complete regression of tumor in 20% of the mice when the initial dose was high (15 mg/kg, i.p.). Human melanoma exhibited a response to MF13 similar to colon cancer. Activity of MF13 in murine hepatoma in vivo was stronger than its precursor m-sarcolysin (p<0.001). Tumor cells in peritoneal cavities of the MF13 treated (s.c.) mice underwent an irreversible apoptosis. Side effects of MF13 were the transient depression of hemopoiesis and loss of body weight, which vanished within 9-10 days. LD50 of MF13 of a single i.p. injection was 27 mg/kg (94 mg/m2), 11 times higher than the therapeutic dose of a single injection.

Overexpression of deletion-mutant epidermal growth factor receptor is associated with altered genotoxic stress-provoked p53 mRNA induction in a human glioblastoma cell line.

A distinct 801-bp deletion mutation of the epidermal growth factor receptor (EGFR) gene is frequently present in primary glioblastoma multiforme (GBM), confers enhanced tumorigenicity in vivo and is prognostic of a shorter interval to clinical relapse. This study sought to investigate whether overexpression of deletion-mutant (delta) EGFR affects genotoxic stress-provoked mRNA inductions of p53 and murine double minute 2 (MDM2), two other genes strongly involved in the pathogenesis of GBM. In a set of human wild-type (wt) p53 GBM cell lines (U-87MG and U-87MG.delta EGFR) that exclusively differ in EGFR expression (endogenous wt EGFR expression and exogenous delta EGFR overexpression, respectively), ultraviolet (UV) light irradiation-mediated EGFR, p53 and MDM2 genotoxic stress-provoked mRNA inductions were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and densitometry of electrophoretically separated and stained RT-PCR products. Although baseline (at 0 J/m2) p53 mRNA expression in U-87MG.delta EGFR was 42-fold reduced, maximum p53 induction (at 8 J/m2) amounted to 130% compared to U-87MG. Thus, ultimate UV light-mediated p53 mRNA induction was 131.5-fold in U-87MG.delta EGFR and 2.8-fold in U-87MG. In contrast, neither wt/delta EGFR nor MDM2 mRNA expressions were significantly inducible, and MDM2 mRNA profiles were essentially the same among U-87MG and U-87MG.delta EGFR. These data suggest that in human GBM overexpression of delta EGFR is associated with differential genotoxic stress-provoked p53 mRNA induction whereas MDM2 mRNA expression is apparently not directly affected by EGFR status.

Detection of MMTV-like LTR and LTR-env gene sequences in human breast cancer.

We have previously reported, using the polymerase chain reaction (PCR), the presence of a 660 bp sequence homologous to the env gene of MMTV in 38% of the human breast cancers studied, but not in normal breasts nor in other tumors or tissues. We have now investigated the presence of MMTV-like LTR sequences in human breast cancer and normal breast tissue. Primers were selected to amplify a 630 bp sequence homologous to MMTV, but not to the endogenous retrovirus HERV-K10. This sequence was detected in 41.5% of the breast cancers and none of the normal breasts. A larger 1.2 kb LTR fragment was also amplified with high homology to MMTV. Finally, a 1.6 kb fragment containing env and LTR sequences was amplified, cloned and sequenced from breast cancer DNA. The human LTRs were highly homologous to MMTV contain enhancer and promoter elements, the glucocorticoid responsive element (GRE) and the superantigen (Sag) sequences. Presence of functional sequences implies involvement in transcriptional regulation, whereas presence of an env-LTR sequence indicates contiguity within the genome of a potential provirus. Their presence in breast cancer DNA, but not in normal tissue, suggest an exogenous origin.

MMTV-like env gene sequences in human breast cancer.

We have previously detected an MMTV env gene-like 660 bp sequence in 38% of human breast cancers, but not in normal tissues or other tumors. In this communication we report the sequences from eleven tumors and three breast cancer cell lines, and compare them to four strains of MMTV and to the known endogenous retroviral sequences. The breast cancer sequences were highly homogenous to the MMTV's, but not to the endogenous sequences suggesting an exogenous origin.

Search for mouse mammary tumor virus-like env sequences in cancer and normal breast from the same individuals.

We have reported previously that a 660-bp sequence homologous to the env gene of the mouse mammary tumor virus, but not to the known endogenous retroviruses, was present in 38% of human breast cancers (Y. Wang et al., Cancer Res., 55: 5173-5179, 1995). A unique 250-bp internal sequence was equally present in formalin-fixed breast carcinoma. It was not detected in normal human breasts or in other tumors. In this study, we have investigated whether this 250-bp env sequence was also present in the formalin-fixed normal tissues of individuals with env sequence-positive breast cancer. Separate paraffin-embedded sections from breast carcinoma and normal breast tissues from the same individual were obtained from the Cooperative Breast Cancer Tissue Registry of the National Cancer Institute. The 250-bp env sequence was detected in 30.1% of the 106 tumors but in only 1 of the 106 normal breast tissues. These results indicate that the sequence is absent in normal tissues and thus is not genetically transmitted. This strongly implies that it is of exogenous origin.

Identification of a proviral structure in human breast cancer.

Involvement of a virus similar to mouse mammary tumor virus (MMTV) in human breast cancer has long been postulated but never demonstrated. We have detected by PCR a 660-bp sequence similar to the env gene of MMTV but not to the known endogenous viruses, in 38% of human breast cancers examined (Wang et al., Cancer Res., 55: 5173-5179, 1995). This sequence was expressed in 66% of the env-positive tumors as detected by reverse transcription-PCR (Wang et al., Clin. Cancer Res., 4: 2565-2568, 1998). In this article we report the amplification of a whole proviral structure from each of two human breast carcinomas that were env positive. Using nested extra-long PCR and primers from specific MMTV sequences, overlapping env-long terminal repeat (LTR), LTR-gag, gag-pol, and pol-env segments were successfully amplified. The 9.9-kb provirus is 95% homologous to MMTV but only 57% to human endogenous retrovirus K10 in 3.5 kb of the gag and pol genes. The provirus displays typical features of a replication competent virus, plus the open reading frame for the superantigen and the glucocorticoid responsive element. Fluorescence in situ hybridization with a 2.7-kb env-LTR sequence of an env-positive breast cancer cell line revealed that the sequence is inserted in several chromosomes but not in chromosomes from normal breast cells. The origin of the MMTV-like sequences is uncertain. Because they are undetectable in normal tissues, because the similarity between the two isolates is high (96%), and because they maintain open reading frames, they appear to be exogenous.

3-m-bromoacetylamino benzoic acid ethyl ester: a new cancericidal agent that activates the apoptotic pathway through caspase-9.

The mechanism underlying the cancericidal activity of 3-m-bromoacetylamino benzoic acid ethyl ester (3-BAABE) was investigated. 3-BAABE exerted a strong cancericidal effect on human leukemia and lymphoma cells (IC(50) < 0.2 microgram/mL) and on cell lines of prostate, colon, ductal, and kidney cancer (IC(50) 0.8 to 0.88 microgram/mL). Multiple drug resistance (MDR) had no effect on the susceptibility of human lymphoma cells to 3-BAABE, since Daudi/MDR(20) and wild-type Daudi cells had a similar susceptibility to the cytotoxic effect of 3-BAABE. The cancericidal effect of 3-BAABE, which was not associated with changes in the cell cycle, was mediated by apoptosis. Thus, cells exposed to 3-BAABE displayed the DNA fragmentation ladder characteristic for apoptosis, associated with a marked increase of the activity of apoptosis effector caspases-3 and -6, which was followed by proteolytic cleavage of DNA fragmentation factor (DFF) and poly(ADP-ribose) polymerase (PARP). Exposure of tumor cells to 3-BAABE increased the activity of apical caspase-9, but had no effect on caspase-8. Complete inhibition of 3-BAABE-induced apoptosis was exerted by LEHD-FMK, a caspase-9 inhibitor. DEVD-FMK, a caspase-3 inhibitor, and VEID-FMK, a caspase-6 inhibitor, partially inhibited 3-BAABE-induced apoptosis, whereas exposure to IETD-FMK, a caspase-8 inhibitor, had no effect. The fragmentation and elevated activity of caspase-9 in 3-BAABE-treated cells and the fact that only an inhibitor of caspase-9 abrogated 3-BAABE-induced apoptosis indicate that 3-BAABE is a distinctive compound that elicits apoptosis through a pathway that is limited specifically to activation of apical caspase-9.

Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo.

PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme which catalyzes the formation of prostaglandins from arachidonic acid, is expressed in prostate cancer specimens and cell lines. To evaluate the in vivo efficacy of a COX-2 inhibitor in prostate cancer, NS398 was administered to mice inoculated with the PC-3 human prostate cancer cell line. MATERIALS AND METHODS: A total of 28 male nude mice were inoculated subcutaneously with 1 million PC-3 cells. Tumors were palpable in all 28 animals 1 week after inoculation and mice were randomized to receive either vehicle (control) or NS398, 3 mg./kg. body weight, intraperitoneally three times weekly for 9 weeks. Tumors were measured at weekly intervals. After a 10-week experimental period, mice were euthanized and tumors were immuno- histochemically assayed for proliferation (PCNA), apoptosis (TUNEL) and microvessel density (MVD) (Factor-VIII-related antigen). Tumor VEGF content was assayed by Western blotting. RESULTS: NS398 induced a sustained inhibition of PC-3 tumor cell growth and a regression of existing tumors. Average tumor surface area from control mice was 285 mm.2 as compared with 22 mm.2 from treated mice (93% inhibition, p <0.001). Immunohistochemical analysis revealed that NS398 had no effect on proliferation (PCNA), but induced apoptosis (TUNEL) and decreased MVD (angiogenesis). VEGF expression was also significantly down regulated in the NS398-treated tumors. CONCLUSIONS: These results demonstrate that a selective COX-2 inhibitor suppresses PC-3 cell tumor growth in vivo. Tumor growth suppression is achieved by a combination of direct induction of tumor cell apoptosis and down regulation of tumor VEGF with decreased angiogenesis

Interleukin-2 plus chemotherapy for patients with metastatic melanoma.

We studied the activity of recombinant interleukin-2 (IL2) in combination with multiagent chemotherapy in the treatment of patients with disseminated malignant melanoma. Patients were randomized to receive the same dose of lymphokine by constant 24 h intravenous infusion (CI) or by subcutaneous bolus (SB) injection. Twenty-two patients, 18 males and four females with a median age of 44 years (range 32-73 years) were randomized to receive IL2 5 million units/m2 once daily by SB injection or by CI, 5 days/week for 2 weeks. All patients received a chemotherapy regimen consisting of lomustine (CCNU) 75 mg/m2 on day 14, bleomycin 10 units/day by CI for 5 days (days 14-19) and cisplatin 75 mg/m2 on day 19. Patients were retreated after a 3 week interval. There were four complete responses and one partial response in the CI arm and two partial responses in the SB arm. The median duration of response was 38 weeks (range 26-107 weeks). The median duration of survival was 6.7 months in non-responders and 11.1 months in responders. The overall response rate was 32%. Since responses were brief and all the responding patients progressed after a median of 38 weeks, the study was terminated before accrual goals were met.

PAR, a novel androgen regulated gene, ubiquitously expressed in normal and malignant cells.

During our work on the mechanism of hormone resistance of prostatic carcinomas, a novel gene that we called PAR (prostate androgen regulated) was isolated from an androgen resistant subline (LNCaP-OM) using a modified representational difference analysis. The complete sequence of the gene cDNA has 1029 nucleotides with a continuous reading frame of 438 bases encoding for 146 amino acids. Its deduced amino acid sequence has motifs for myristoylation and phosphorylation by protein kinase C. The PAR gene was overexpressed in all prostatic carcinoma cell lines studied (LNCaP, DU145, PC3 and LNCaP-OM) compared to the normal prostatic tissue. Furthermore, its expression was higher in androgen resistant prostate cancer lines DU145, PC3 and LNCaP-OM, in comparison to androgen sensitive LNCaP cells. The expression of this gene was down regulated by androgens in androgen sensitive prostate cells, but not in the hormone resistant cell lines. The PAR mRNA was detected in all 29 normal human tissues studied and overexpressed in most (67%) of their malignant counterparts. The PAR expression was higher in MCF7 and T47D breast cancer cell lines, as well as in all primary breast tumors studied compared to their normal tissue counterparts. The biological function of this gene is still unknown, but its ubiquitous expression in normal tissues and its overexpression in some malignancies suggest the PAR involvement in certain basic cellular processes and possibly, in malignant transformation.

Marked inhibition of glioblastoma target cell tumorigenicity in vitro by retrovirus-mediated transfer of a hairpin ribozyme against deletion-mutant epidermal growth factor receptor messenger RNA.

OBJECT: The goal of this study was to evaluate the activity of certain hairpin ribozymes against deletion-mutant epidermal growth factor receptor (deltaEGFR) messenger (m)RNA in glioblastomas multiforme (GBMs). A distinct 801-bp deletion mutation associated with amplification of the EGFR gene is present in a large subgroup of primary GBMs and confers enhanced tumorigenicity in vivo. As a result of the deletion mutation, the fusion junction of the gene is created directly upstream of a GTA triplet, which is subsequently transcribed into a ribozyme target codon (GUA). METHODS: In attempts to intercept deltaEGFR gene expression at the mRNA level, the authors designed three different hairpin ribozymes derived from the negative strands of satellite RNAs in tobacco ringspot virus, chicory yellow mottle virus (sCYMV1), and arabis mosaic virus against this target and evaluated their efficiency and specificity in a cell-free system. The sCYMV1, identified as the most active anti-deltaEGFR hairpin ribozyme motif, was cloned into the retroviral plasmid N2A+tRNAi(met). High-titer recombinant retrovirus-containing supernatants (> 10(5) colony-forming units/ml) derived from an amphotropic GP+envAM 12 packaging cell line transfected with the N2A+tRNAi(met)-anti-deltaEGFR-sCYMV1 construct were used to introduce the sCYMV1 hairpin ribozyme into U-87MG.deltaEGFR glioblastoma cells, which overexpress exogenous deltaEGFR. Using a virus/target cell ratio of 40:1 in the absence of drug selection, the ribozyme transfer resulted in a greater than 90% reduction of deltaEGFR mRNA levels, a 69% inhibition of deltaEGFR-mediated proliferation advantage, and a greater than 95% decrease of colony formation in soft agar under relative serum starvation conditions in vitro; transfer of a control mutant ribozyme that was rendered incapable of cleaving its target yielded none of these effects. CONCLUSIONS: These findings indicate that the anti-deltaEGFR-sCYMV1 hairpin ribozyme is capable of specifically inhibiting the expression of deltaEGFR and reversing the deltaEGFR-associated malignant phenotype of GBM cells. This strategy may constitute a promising gene therapy approach for a molecularly defined subgroup of GBMs.

Inhibitory effect of telomere-mimic phosphorothioate oligodeoxy nucleotides (S-ODNS) on human tumor cell lines.

To clarify the inhibitory effect of telomere-mimic oligonucleotides on human cancer cell lines, we synthesized 18-mers (18T; n = 3), 24-mers (24T; n = 4) and 30-mers (30T; n = 5) of telomere-mimic phosphorothioate oligodeoxy nucleotides [5'-d(TTA GGG)n-3'] and examined their effects on the proliferation of human tumor cells by XTT assay. After 7 days of continuous exposure to 24T and 30T at concentrations ranging from 0.1 to 10 microM, concentration-dependent cell growth inhibition was observed in MCF-7 clone E3, ZR-75-1, MDA-MB 231, Colo 201 and WiDr. All of these cell lines highly expressed telomerase using the telomeric repeat amplification protocol. None of these tumor cell lines were affected by 18T. In MCF-7, ZR-75-1 and Colo 201 cell lines, a more than 50% growth inhibition was obtained by 3 microM of 24T and 30T whereas, in MDA-MB 231 and WiDr cell lines, cell growth inhibition was less than 50%. 30T was more effective than 24T. Estrogen-dependent growth of both MCF-7 and ZR-75-1 was inhibited by 3 microM of 24T and 30T, however, in the absence of estrogen, no growth inhibition was seen. The MCF-10A cell line, which was developed from normal human breast tissue and expressed telomerase only weakly, was inhibited by 10 microM of 18T. In conclusion, these observations indicate that S-ODNs inhibit tumor growth in cell lines expressing telomerase in a concentration-dependent manner and that cell growth inhibition is dependent on the length of S-ODNs. In addition, the short-length S-ODNs may inhibit growth of cells weakly expressing telomerase, but not of cells with high telomerase expression.

Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor.

We previously reported that a 660-bp sequence that is homologous to the env gene of the mouse mammary tumor virus (MMTV) but not to endogenous retroviruses or to other known genes was present in 38% of human breast cancers and in some breast cancer cell lines studied (Y. Wang et al., Cancer Res., 55: 5173-5179, 1995). Here, we have investigated whether the MMTV-like sequences were associated with the clinical, pathological, and molecular parameters that have been reported to define two subsets of human breast cancers. Archival breast carcinoma samples were analyzed for four clinical parameters, obtained from patients' records, and for six pathological characteristics. Expression of c-erbB-2, p53, bcl-2, progesterone receptor, laminin receptor, and cathepsin D was detected by immunochemistry using monoclonal antibodies. PCRs were used to amplify 250 bp of the MMTV env gene-like sequence. The chi2, log-rank, and generalized Wilcoxon tests were used to analyze the data. The MMTV env gene-like sequence was detected in 37.7% of the samples. The presence of this sequence was not significantly associated with any of the pathological clinical or biological parameters studied. It did correlate, however, with expression of the laminin receptor, a marker for invasiveness and poor prognosis. This is the first phenotypic characterization of human breast cancers containing retroviral sequences.