Novel Family of Gynecologic Cancer Antigens Detected by Anti‐HIV Antibody

Rakowicz-Szulczynska, Ewa M.; McIntosh, David G.; Morris, Peter J.; Smith, M. I.

doi:10.1155/s1064744994000608

Cited by 7 publications

(8 citation statements)

References 17 publications

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“…The anti-HIV-1 gp120 MAb (amino acids 308 to 322) was purchased from Du Pont. The ability of that MAb to detect a cancer antigen was reported before (25,26). Control antibodies, which do not recognize cancer antigens, including another epitope-specific anti-HIV-1 gp120 MAb (25,27) and an anti-HIV-1 p25 MAb, were from Du Pont.…”

Section: Cell Lines Breast Carcinoma Cell Linesmentioning

confidence: 73%

“…Tissue fractionation. Fractionation of tissue was described before (25)(26)(27)(28)(29). Briefly, cancer and normal tissue samples were homogenized in 0.35 M sucrose-10 mM KCl-1.5 mM MgCl 2 -10 mM Tris-HCl (pH 7.6)-0.12% Triton X-100-12 mM 2-mercaptoethanol and centrifuged at 600 ϫ g for 10 min.…”

Section: Cell Lines Breast Carcinoma Cell Linesmentioning

confidence: 99%

“…We have recently identified a new class of breast and gynecological cancer markers, which have been named Rakowicz markers or, briefly, RAK markers (25)(26)(27)(28)(29)(30). RAK antigens p120, p42, and p25 express epitopes in common with envelope protein gp120 of human immunodeficiency virus type 1 (HIV-1) and can be detected either by an epitope-specific anti-HIV-1 gp120 monoclonal antibody (MAb) (25)(26)(27), or by MAb RAK-BrI, which is directed against breast cancer (28,29). RAK antigens are absent in normal breast tissue and other normal tissues (28), which suggests the strong diagnostic potential of these unique markers.…”

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confidence: 99%

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Human Immunodeficiency Virus Type 1-Like DNA Sequences and Immunoreactive Viral Particles with Unique Association with Breast Cancer

Rakowicz-Szulczynska

Jackson²,

Szulczynska³

et al. 1998

Clin Diagn Lab Immunol

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RAK antigens p120, p42, and p25 exhibit molecular and immunological similarity to the proteins encoded by human immunodeficiency virus type 1 (HIV-1) and are expressed by 95% of breast and gynecological cancer cases in women and prostate cancer cases in men. The binding of an epitope-specific anti-HIV-1 gp120 monoclonal antibody (MAb) (amino acids 308 to 322) to cancer RAK antigens has been found to be inhibited by a peptide derived from variable loop V3 of HIV-1. Breast cancer DNAs of 40 patients were PCR amplified with HIV-1 gp41-derived primers, and all of the samples were found to be positive. The DNA fragments amplified in seven blindly selected breast cancer samples were sequenced. The breast cancer DNA sequences showed at least 90% homology to the HIV-1 gene for gp41. Antisense oligonucleotides complementary to the HIV-1-like sequences inhibited reverse transcriptase activity and inhibited the growth of breast cancer cells in vitro. Viral particles detected in breast cancer cell lines were strongly immunogold labeled with the anti-HIV-1 gp120 MAb. The results obtained strongly suggest that the long-postulated breast cancer virus may, in fact, be related to HIV-1.

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Section: Cell Lines Breast Carcinoma Cell Linesmentioning

confidence: 73%

Section: Cell Lines Breast Carcinoma Cell Linesmentioning

confidence: 99%

mentioning

confidence: 99%

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Human Immunodeficiency Virus Type 1-Like DNA Sequences and Immunoreactive Viral Particles with Unique Association with Breast Cancer

Rakowicz-Szulczynska

Jackson²,

Szulczynska³

et al. 1998

Clin Diagn Lab Immunol

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“…RAK antigens p120, p42, and p25 are expressed in cancers of the reproductive organs but are absent in normal tissues and in the majority of tissues adjacent to the cancer (21,22,24,26,28,29). Why cancers of different histological structures, which originated from completely different tissues, all express these unique proteins remained for a long time a medical and biological puzzle.…”

Section: Discussionmentioning

confidence: 99%

“…The current study concentrated on gynecological cancer, which was found previously to contain HIV-1-like antigens (26,29). RAK antigens were found to be expressed by 95% of ovarian, uterine, and cervical cancer cases, and the HIV-1-like segments of uterine and ovarian cancer DNA exhibit over 90% homology to HIV-1.…”

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confidence: 99%

Relevance of the Viral RAK Alpha Gene in Diagnosis of Malignant Versus Nonmalignant Tumors of the Ovary and Uterus

Rakowicz-Szulczynska

2000

Clin Diagn Lab Immunol

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Human immunodeficiency virus type 1 (HIV-1)-like antigens RAK (named after the inventor E. M. Rakowicz) p120, p42, and p25, as well as HIV-1-like segments of cancer DNA (RAK gene alpha), have been found before in breast and prostate cancers. The present study focused on determining the value of markers RAK in the diagnosis and prognosis of gynecological cancer. Expression of RAK antigens in ovarian, uterine, cervical, and vulvar cancer, in benign tumors, in tissues adjacent to cancer, and in normal tissues was tested by Western blot hybridization of the electrophoretically separated proteins with monoclonal antibody RAK BrI. The RAK alpha gene was PCR amplified with HIV-1-derived primers SK68 and SK69. RAK antigens p120, p42, and p25 were found in 95% of ovarian, uterine, and cervical cancer cases and in 75% of vulvar cancer cases. The RAK alpha gene was expressed in 100% of cancer cases, in approximately 25% of benign ovarian tumors, and in 40% of benign tumors of the uterus. DNA sequences amplified in all cancer cases exhibited more than 90% homology to HIV-1 gp41 and were encoded for the functional peptide. DNA sequences found in benign tumors contained frameshift mutations and encoded truncated or nonfunctional peptides. Such sequences have not been amplified in normal tissues. RAK antigens and the RAK alpha gene seem to belong to a lentivirus type that is highly related to HIV-1. Beyond the diagnostic value of RAK markers, future cloning of the full viral genome would lead to a better understanding of the etiology of malignant and nonmalignant tumors of reproductive organs and to the development of novel therapeutic approaches.Cancers of the reproductive organs are the most common malignancies in women (7,13,19). Prognostic factors for those patients are directly dependent on the stage of the cancer at diagnosis. Earlier detection of breast, ovarian, cervical, or endometrial cancer would significantly increase survival rates of female patients (9,20,30). Only 10% of breast and 5% of ovarian cancer cases have a documented inherited pattern, associated mainly with the mutated genes BRCA (15,18,34) or the oncogene Her-2/Neu (31).Except for cervical cancer, which is predominantly associated with human papillomavirus (HPV) (2,8,14,17), a viral etiology of other types of female reproductive tract cancers remains unverified. However, the fact that the majority of papillomavirus-infected women do not develop cervical cancer strongly implies that HPV may be an important cofactor, but not the direct cause, of that cancer. Recent studies of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma (3) strongly suggest that the role of retroviruses in human cancer was somehow underestimated for a long time.Viral particles (4, 5, 6, 10, 11, 16) and DNA sequences (1, 32, 33) with homology to the mouse mammary tumor virus (MMTV) have been observed in breast cancer for some time. Since MMTV-like sequences are present in cancer patients, as well as in healthy patients, an involvement of this virus in the etiology o...

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