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A retroviral link to human tobacco-related lung cancer?

Institution: University of California, Los Angeles
Investigator(s): Sanford Barsky, M.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8IT-0046 Award: $74,500
Subject Area: Cancer
Award Type: Inno Dev & Exp Awards (IDEAS)

Initial Award Abstract
Peripheral adenocarcinoma (PAC) and bronchioloalveolar carcinoma (BAC) are forms of lung cancer whose cause is not completely known and whose link to either main stream tobacco smoking or second hand smoking not well understood. While certain types of lung cancer which are strongly linked to smoking like squamous cell carcinoma and small cell carcinoma have shown an overall decrease in incidence during the past decade (due in part to smoking cessation programs), peripheral adenocarcinomas (PACs) and bronchioloalveolar lung cancers (BACs) have shown exponential increases. These increases have been observed equally in both smokers as well as non-smokers. These observations suggest that either different etiological factors exist (other than main stream or second hand smoke) that cause PACs and BACs or that different co-factors stimulate the harmful effects of main stream or second hand smoke and make them more potent in causing PAC/BAC. Some of the distinguishing features of PAC/BAC include its peripheral location in the lung, its association with scarring, its comparatively high female/male ratio, and its high incidence of occurring in multiple locations in the lung (especially BAC). Unlike other forms of lung cancer, PAC/BAC naturally occurs in cats and sheep, the latter disease of which is caused by a virus. In our initial studies, antibodies made to a protein of this virus were able to recognize a related protein in our human cases of PAC/PAC but not in other types of lung cancer nor in normal lung. More surprisingly, in our subsequent studies, the specific viral gene called gag which gives rise to this protein was found to be expressed in the same cases of human PAC/BAC.

These findings raise several intriguing possibilities: 1) a virus causes or predisposes, along with smoking, to PAC/BAC in humans; 2) activation and expression of a viral gene which normally resides within our cells is an important step leading to PAC/BAC lung cancer; 3) this viral gene has nothing to do with the cause of lung cancer but is a marker of an important cellular pathway involved in lung cancer development. The present study will address each of these possibilities.

Feline bronchioloalviolar lung carcinoma (BAC) shares common properties with sheep and human BAC
Periodical: Experimental Biology Index Medicus:
Authors: Grossman D, Hiti A, McNiel F, O'Connell J, Shao Z, Barsky SH ABS
Yr: 1999 Vol: Nbr: Abs: Pg:

Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumors
Periodical: European Respiratory Journal Index Medicus:
Authors: De las Hera M, Barsky SH, Hasleton P, et al ART
Yr: 2000 Vol: 15 Nbr: Abs: Pg: 330-332

Comparative oncological studies of feline bronchioloalveolar lung carcinoma, its derived cell line and xenograft.
Periodical: Cancer Research Index Medicus:
Authors: Grossman DA, Hiti AL, McNiel EA, Ye Y, Alpaugh ML, Barsky SH ART
Yr: 2002 Vol: 62 Nbr: Abs: Pg: 3826-3833

Establishment of an immortalized cell line and transplantable xenograft from a bronchiolaolveolar lung carcinoma of a cat.
Periodical: American Journal of Veterinary Research Index Medicus:
Authors: Grossman DA, McNiel EA, Hackett TB, Barsky SH ART
Yr: 2002 Vol: 63 Nbr: Abs: Pg: 1745-1753